In 1950, Scully joined Barber and Connie Desmond in the Brooklyn Dodgers’ radio and television booths. When Barber got into a salary dispute with World Series sponsor Gillette in 1950, Scully took Barber’s spot for the 1950 World Series. At the age of 23, Scully became the youngest person to broadcast a World Series game (a record that stands to this day). Barber left the Dodgers after the 1950 Brooklyn Dodgers Season to work for the New York Yankees. Scully eventually became the Dodgers’ principal announcer. Scully announced Dodgers games in Brooklyn until 1957, after which the club moved to Los Angeles. During that time, Dodgers broadcasts were heard over WMGM radio (1050) on the AM dial, as well as WOR-TV (channel 9) both in New York.

In 1964, the New York Yankees offered Scully the job to replace the recently fired Mel Allen as their lead play-by-play announcer. Scully declined the offer and chose to remain with the Dodgers. By 1976, his popularity in Los Angeles had become such that Dodger fans voted him the “most memorable personality” in the history of the franchise.

Before 1966, local announcers exclusively called the World Series. Typically, the Gillette Company, the Commissioner of Baseball and NBC television would choose the announcers, who would represent each of the teams that were in the World Series for the respective year. For the 1966 World Series, Curt Gowdy called half of each game before ceding the microphone to Vin Scully in Los Angeles, and Chuck Thompson in Baltimore. Scully was not satisfied with the arrangement as he said “What about the road? My fans won’t be able to hear me.” In Game 1 of the 1966 World Series, Scully called the first 4½ innings. When Gowdy inherited the announcing reins, Scully was so upset that he refused to say another word.

Besides his sportscasting work, Scully was the uncredited narrator for the short-lived NBC sitcom Occasional Wife. Scully also co-hosted the Tournament of Roses Parade with Elizabeth Montgomery for ABC in 1967, served as the host for the NBC game show It Takes Two in 1969–70, and in 1973 hosted The Vin Scully Show, a weekday afternoon talk-variety show on CBS. In 1977, he hosted the prime-time Challenge of the Sexes for CBS.

In 1970, ABC Sports producer Roone Arledge tried to lure Scully to his network to call play-by-play for the then-new Monday Night Football games, but Scully’s commitment to the Dodgers forced him to reject the offer. Instead, the role went to Keith Jackson for the initial year, before being replaced by Frank Gifford (from 1971 to 1985, when Gifford was in return, replaced by Al Michaels while Gifford converted into a color commentator up until 1997).

In 1972, Scully’s 35-year-old wife, Joan Crawford, died of an accidental medical overdose; the couple had been married for 15 years. In late 1973, he married Sandra Hunt, who had two children of her own, and they soon had a child together. Scully’s eldest son, Michael, died in a helicopter crash at the age of 33 while working for the ARCO Transportation Company. He was inspecting oil pipelines for leaks near Fort Tejon, California in the immediate aftermath of the Northridge earthquake in January 1994. Although Michael’s death still haunts him, Scully, a devout Roman Catholic, has said in numerous interviews that he credits his religious faith and being able to dive back into his work with helping him ease the burden and grief from losing his wife and son. He has encouraged devotion to the Virgin Mary, saying, “Her prayers are more powerful than those of the rest of heaven combined. No one was closer or more devoted to Christ on earth, so it only makes sense to see the same thing in heaven. Now, the Blessed Virgin seeks to help her spiritual children get home to spend eternity with her Son.” In 2016, Scully narrated an audio recording of the Rosary for Catholic Athletes for Christ in which he recites the Rosary mysteries and leads a group of responders.

In 1977, Scully began his first of two stints calling baseball for CBS Radio, broadcasting the All-Star Game through 1982 (usually paired with Brent Musburger) and the World Series from 1979 to 1982 (alongside Sparky Anderson).

Scully decided to leave CBS in favor of a job calling baseball games for NBC (beginning in 1983) following a dispute over assignment prominence (according to CBS Sports producer Terry O’Neil, in the book The Game Behind the Game). CBS decided going into the 1981 NFL season that John Madden, whom CBS had hired in 1979 and who had called games alongside Frank Glieber and Gary Bender his first two years, was going to be the star color commentator of their NFL television coverage. But they had trouble figuring out who was going to be his play-by-play partner, since Scully was in a battle with CBS’ lead play-by-play announcer Pat Summerall for the position. At the time Scully was the number two announcer for CBS, a position he had held since 1975, and was calling games alongside the former Kansas City Chiefs head coach Hank Stram, who had been promoted from CBS’ number three broadcast team alongside Curt Gowdy.

Like Red Barber and Mel Allen in the 1940s, Scully retained his credentials in football even as his baseball career blossomed. From 1975 to 1982, Scully announced National Football League telecasts for CBS Sports, teaming with several different color analysts including Sonny Jurgensen, Paul Hornung, Alex Hawkins, George Allen, Jim Brown, John Madden, and Hank Stram. One of his most famous NFL calls was that of Dwight Clark’s touchdown catch in the NFC Championship Game on January 10, 1982 (which Scully called with Stram as his final NFL telecast for CBS), that put the San Francisco 49ers into Super Bowl XVI.

After the eighth week of the NFL season, CBS Sports decided that Summerall meshed more with Madden than Scully did and it named him to be the announcer who would call Super Bowl XVI for CBS on January 24, 1982, at the Pontiac Silverdome. An angry Scully, who felt that his intelligence had been insulted by the move, was assigned as a consolation prize that year’s NFC Championship Game, which he called alongside Stram. Summerall took Stram’s place alongside Jack Buck to call the game over CBS Radio.

Scully received the Ford Frick Award from the National Baseball Hall of Fame in 1982, and was honored with a Lifetime Achievement Emmy Award for sportscasting and induction into the National Radio Hall of Fame in 1995. The National Sports Media Association (formerly the National Sportscasters and Sportswriters Association) named Scully as National Sportscaster of the Year four times (1965, 1978, 1982, 2016) and California Sportscaster of the Year 33 times, and inducted him into its Hall of Fame in 1991. He was the 1992 Hall of Fame inductee of the American Sportscasters Association, which also named him Sportscaster of the Century (2000) and top sportscaster of all-time on its Top 50 list (2009). The California Sports Hall of Fame inducted Scully in 2008. Scully was inducted into the NAB Broadcasting Hall of Fame in 2009. On May 11, 2009, he was awarded the Ambassador Award of Excellence by the LA Sports & Entertainment Commission.

After the 1989 season, NBC (along with ABC, with whom NBC had shared baseball coverage since 1976), lost the television rights to cover Major League Baseball to CBS. For the first time since 1946, NBC would not televise baseball. In the aftermath, Scully said of NBC losing baseball, “It’s a passing of a great American tradition. It is sad. I really and truly feel that. It will leave a vast window, to use a Washington word, where people will not get Major League Baseball and I think that’s a tragedy. … It’s a staple that’s gone. I feel for people who come to me and say how they miss it and, I hope, me.”

After the National League Championship Series in 1989, Scully’s NBC contract was up and he left to focus primarily on his duties with the Dodgers. Scully also returned to being the national radio announcer for the World Series, since CBS Radio gave him the position that Jack Buck had vacated in order to become the primary announcer of CBS’s television coverage of Major League Baseball. Scully’s first assignment was the 1990 World Series and he remained in that role until 1997, working with Johnny Bench for the first four years and Jeff Torborg for the final three. After ESPN Radio acquired the World Series radio rights from CBS in 1998, Scully was offered a continued play-by-play role but declined. Instead, ESPN Radio used Sunday Night Baseball television play-by-play man Jon Miller for their World Series coverage for the next thirteen years.

From 1991 to 1996, Scully broadcast the annual golf Skins Game for ABC, having previously called the event for NBC from 1983 to 1989. He also called the Senior Skins Game for ABC from 1992 to 2000, as well as various golf events for TBS during this period. In 1999, Scully was the master of ceremonies for MasterCard’s Major League Baseball All-Century Team before the start of Game 2 of the World Series.

Unlike the modern style in which multiple sportscasters have an on-air conversation (usually with one functioning as play-by-play announcer and another as color commentator), Scully and his broadcast partners Jerry Doggett (1956–1987) and Ross Porter (1977–2004) called games solo with Scully working the entire game except for the 3rd and 7th innings. When Doggett retired after the 1987 season, he was replaced by Hall-of-Fame Dodgers pitcher Don Drysdale, who previously broadcast games for the California Angels. Drysdale died in his hotel room following a heart attack before a game against the Montreal Expos in 1993, resulting in a very difficult broadcast for Scully and Porter, who were told of the death but could not mention it on-air until Drysdale’s family had been notified and the official announcement of the death made. Scully announced the news of his death by saying, “Never have I been asked to make an announcement that hurts me as much as this one. And I say it to you as best I can with a broken heart.”

Scully was the announcer in the popular Sony PlayStation–exclusive MLB video game series by 989 Sports for a number of years. Scully has since retired from announcing for video games, with his final year involving the video game MLB 2005. Matt Vasgersian, Eric Karros, and Steve Lyons (and formerly Dave Campbell and Rex Hudler) have since taken over as the lead announcers in the video game series, which was retitled MLB: The Show. Scully appears as himself in the 1999 film For Love of the Game, has a brief cameo (along with then-Dodgers partner Jerry Doggett) in the 1961 film Bachelor in Paradise, appears as a CBS news reporter in the 1960 film Wake Me When It’s Over, provides the opening narration in the 1966 film Fireball 500, and can be heard calling baseball games in the films Experiment in Terror (1962), Zebra in the Kitchen (1965), The Party (1968), and The Bucket List (2007), as well as in episodes of TV series including General Electric Theater, Alcoa Premiere, Mister Ed, The Joey Bishop Show, The Fugitive, Highway to Heaven, and Brooklyn Bridge. The surname of the Dana Scully character on the television show The X-Files is an homage to Vin Scully, as the show’s creator Chris Carter is a Dodgers fan; Scully himself can be heard calling a game in the Season 6 episode “The Unnatural”.

The Dodgers management announced in February 2006 that it had extended Scully’s contract through the 2008 baseball season for about $3 million per year. For health reasons, beginning around 2005, Scully no longer called most non-playoff games played east of Phoenix. Exceptions to this rule were the 2007 opening series in Milwaukee, a series against the Chicago Cubs in 2007, a series against the Boston Red Sox in 2010, and the series in Australia against the Diamondbacks that opened the 2014 baseball season. He was also not normally scheduled to announce Dodgers games (on either radio or TV) that were televised by ESPN on Sunday Night Baseball or by Fox on the Saturday Game of the Week.

WFUV, the Fordham University radio station that Scully helped found, presents an annual Vin Scully Lifetime Achievement Award for sports broadcasting. Scully himself was the inaugural recipient of the award in 2008.

Scully served as the Grand Marshal for the 2014 Tournament of Roses Parade. Also, he participated aboard the Los Angeles Dodgers’ 50th anniversary float in the 2008 Tournament of Roses Parade.

An unauthorized biography of Scully, Pull Up a Chair: The Vin Scully Story, written by Curt Smith, was published in 2009.

For many years, Scully reportedly did not attend (or even watch on TV) a baseball game he was not announcing. It was not until 2004, when he and then-Dodgers owner Frank McCourt attended a game at Fenway Park, that Scully went to a pro baseball game as a spectator. Scully and McCourt took in another game at Fenway in 2010.

Scully missed most of the Dodgers’ opening homestand of the 2012 MLB season (the first five out of six games) because of an illness. Scully returned to the announcers’ booth on April 15, 2012, which was the 65th anniversary of Jackie Robinson’s breaking of the color barrier in baseball. It was just the second time in 35 years the legendary sports broadcaster had missed a Dodger Stadium home opener: The first time was when he was busy broadcasting the Masters golf tournament for CBS in 1977.

On September 5, 2014, Bud Selig presented him with the Commissioner’s Historic Achievement Award. He was the 14th recipient and (after Rachel Robinson) second non-player to receive the award, which was created to recognize accomplishments and contributions of historical significance to the game of baseball.

On August 28, 2015, the Dodgers announced—via a series of cue cards presented by comedian Jimmy Kimmel on the Dodger Stadium video board—that Scully would be back for the 2016 season, his 67th with the Dodgers. At a press conference August 29, Scully said 2016 would probably be his final year. “I mean, how much longer can you go on fooling people? So yeah, I would be saying, ‘Dear God, if you give me next year, I will hang it up.'”

Scully’s final regular season game broadcast from Dodger Stadium occurred on September 25, 2016. His final game was broadcast from San Francisco’s AT&T Park on October 2, 2016.

As of his final season in 2016, Scully called approximately 100 games per season (all home games and select road games in San Francisco, San Diego, and Anaheim) for both flagship radio station KLAC and television outlet SportsNet LA. Scully was simulcast for the first three innings of each of his appearances, then announced the remaining innings only for the TV audience. If Scully was calling the game, Charley Steiner took over play-by-play on radio beginning with the fourth inning, with Rick Monday as color commentator. If Scully was not calling the game, either Joe Davis or Steiner would call the entire game on television with Orel Hershiser and Nomar Garciaparra on color commentary. while Monday, now doing play-play, joined Kevin Kennedy on radio. Through 2014, in the event the Dodgers were in postseason play, Scully called the first three and last three innings of each radio broadcast alone, with Steiner and Monday handling the middle innings.

On January 31, 2016, Scully announced that he planned to retire from broadcasting after the conclusion of the 2016 season; his final game was the team’s October 2 finale at San Francisco. Scully left open the possibility of calling postseason games (but not the World Series) if the Dodgers were to advance; in September, however, Scully stated that he would retire after the end of the regular season and not call postseason games because he did not want to “say goodbye 12 different times.” Scully was assigned a total of six road games for the 2016 season: the opening game in San Diego, two games in Anaheim, and the entirety of the three-game regular-season closing series in San Francisco.

His final home game was on September 25, 2016, against the visiting Colorado Rockies. The Dodgers ended up winning on a 10th inning walk-off home run by Charlie Culberson and in doing so clinched the NL West Division title. The final broadcast of his career was the Dodgers’ October 2 game at AT&T Park against the San Francisco Giants. Scully’s commentary during his final game was simulcast in its entirety on radio, instead of only the first three innings. After the game, he offered a prayer and a final message:

Several honors were bestowed in 2016, Scully’s final year. On January 29, the Los Angeles City Council voted unanimously to rename Elysian Park Avenue, which changed the address of Dodger Stadium to 1000 Vin Scully Ave. July 8 was dubbed “Vin Scully Day” by the acting governor of California, Kevin de León. During the pre-game ceremony on September 23, 2016, Los Angeles Mayor Eric Garcetti presented Vin Scully with the key to the city. On November 22, Scully received the Presidential Medal of Freedom, the highest civilian honor given by the President of the United States.

In 2017, Scully’s commentary for the final Brooklyn Dodgers/New York Giants game in 1957 was selected for preservation in the National Recording Registry by the Library of Congress as being “culturally, historically, or artistically significant.” Also in 2017, Scully won the Icon Award as part of that year’s ESPY Awards ceremony.

In November 2017, Scully stated that he would “never watch another NFL game again” due to some of the league’s players kneeling during the playing of the national anthem prior to games.

The following year, the Dodgers advanced to the World Series for the first time in 29 years. Despite many Dodgers fans petitioning Scully to come out of retirement, including Fox Sports announcer Joe Buck (who was quoted as saying, “I swear on my late father, to have Vin come do some of the series with us and in my place would be an honor”), Scully declined, preferring to keep a low profile and responding that “I’ve done enough of them.” Scully’s decision echoed that of Myron Cope, who had retired after the 2004 season as the Pittsburgh Steelers color commentator, only to see the team advance to Super Bowl XL the following season and an unsuccessful fan petition to have Cope call that game. Scully did, however, take part in the first pitch ceremony prior to Game 2 with Steve Yeager and Fernando Valenzuela, teammates on the Dodgers team that won the 1981 World Series. In 2020, he was auctioning sports memorabilia in part to donate to neuromuscular research.