Brock hit for a .189 batting average in his first year of college baseball, but improved the following year to hit for a .500 average. Southern University won the National Association of Intercollegiate Athletics’ baseball championship during his junior year, and Brock was selected for the United States baseball team in the 1959 Pan American Games. When Brock decided to try for a professional baseball career, he traveled to St. Louis to try out for the Cardinals, but the scout who had recommended him was in Seattle to sign Ray Washburn. He then decided to try out for the Chicago Cubs, who signed him as an amateur free agent in 1960. Assigned to play for the St. Cloud Rox, Brock won the 1961 Northern League batting championship with a .361 batting average.

Brock made his major league debut with the Cubs on September 10, 1961, at the age of 22. In his rookie season of 1962, Brock became one of four players to hit a home run into the center-field bleachers at the old Polo Grounds in New York City since its 1923 reconstruction. His blast came against Al Jackson in the first game of a June 17 doubleheader against the New York Mets and was one of two that cleared the wall in consecutive days, with Hank Aaron’s coming the very next day. Joe Adcock was the first to hit a ball over that wall, in 1953. Babe Ruth reached the old bleachers (a comparable distance) before the reconstruction. Brock was not known as a power hitter, though he aspired to be one.

Brock had great speed and base running instincts, but the young right fielder failed to impress the Cubs management, hitting for only a combined .260 average over his first two seasons. In 1964 after losing patience with his development, the Cubs gave up on Brock and made him part of a trade with the St. Louis Cardinals. The June 15 deadline deal for pitcher Ernie Broglio saw Brock, Jack Spring, and Paul Toth head to St. Louis for Broglio, Bobby Shantz, and Doug Clemens. Cardinals general manager Bing Devine specifically sought Brock at the insistence of Cardinals’ manager Johnny Keane to increase team speed and solidify the Cardinals’ lineup, which was struggling after the retirement of left fielder Stan Musial in 1963. At the time, many thought the deal was a heist for the Cubs. Broglio had led the National League in wins four years earlier, and had won 18 games the season before the trade.

Brock remained best known for base-stealing and starting Cardinals rallies. He was said to have disliked Wills’ method of base-stealing, instead shortening his leads and going hard. He was also an early student of game films. In 1964, Brock acquired a movie camera and filmed opposing pitchers from the dugout to study their windups and pickoff moves to detect weaknesses he could exploit.

In 1966, Brock ended Maury Wills’ six-year reign as the National League’s stolen base champion with 74 steals. In David Halberstam’s book, October 1964, the author stated manager Johnny Keane asked Brock to forgo hitting home runs in favor of stealing bases. Brock went on to lead the National League in stolen bases eight times within a nine-year span between 1966 and 1974 (former teammate Bobby Tolan led the league in steals in 1970).

Brock began the 1967 season by hitting five home runs in the first four games of the season, becoming the first player to do so (Barry Bonds tied this record in 2002). He was hitting for a .328 average by mid-June to earn the role as the starting left fielder for the National League in the 1967 All-Star Game. After suffering through a mid-season slump, he recovered to finish the season with a career-high 206 hits and a .299 batting average while leading the league in stolen bases and runs scored as the Cardinals won the National League pennant by ten and a half games. Brock became the first player to steal 50 bases and hit 20 home runs in the same season. In the 1967 World Series, Brock hit for a .414 average, scored 8 runs, and set a World Series record with seven stolen bases as the Cardinals defeated the Boston Red Sox in seven games.

The Cardinals won the National League pennant for a second consecutive year in 1968 as Brock once again led the league in stolen bases as well as in doubles and triples. In the 1968 World Series against the Detroit Tigers, Brock had three stolen bases in Game 3 and contributed a double, triple, home run, and four runs batted in during Game 4 to help the Cardinals build a three-games to one advantage over the Tigers. The Cardinals appeared to be on the verge of winning a second consecutive World Series, going into the fifth inning of Game 5 with a 3–2 lead. Although Brock’s base running abilities had proven to be a factor in the previous four games, his carelessness may have cost the Cardinals a run. After Brock had hit a double, he tried to score standing up on Julián Javier’s single to left, but Willie Horton threw him out with a strong throw to home plate. Detroit rallied for three runs in the seventh inning as Mickey Lolich shut out the Cardinals for the final eight innings to win the game for the Tigers. In Game 7, Brock had another crucial miscue when he was picked off base by Lolich, extinguishing a possible Cardinals rally. The Tigers rallied from being down three games to one behind the excellent pitching of Mickey Lolich to win the series. Brock once again stole seven bases and was the leading hitter in the series, posting a .464 batting average with 6 runs and 5 runs batted in.

Brock’s .391 World Series batting average is the highest for anyone who played over 20 series games. His 14 stolen bases in World Series play are also a series record. Brock’s 13 hits in the 1968 World Series tied a single-series record previously made by Bobby Richardson in 1964 against his Cardinals’ team, and was in turn later tied in 1986 by Marty Barrett.

Brock received numerous awards during his playing career. In January 1968 he was named the recipient of the Babe Ruth Award as the outstanding player in the 1967 World Series. Brock was honored with The Sporting News Player of the Year Award in 1974. In the wake of his record-setting 118 stolen bases during the 1974 season, Brock was named the winner of the Roberto Clemente Award in March 1975, for best exemplifying the game of baseball both on and off the field. In 1977 he was awarded the Lou Gehrig Memorial Award as the player who best exemplified Lou Gehrig’s ability and character. In 1978, the National League announced that its annual stolen base leader would receive the Lou Brock Award, making Brock the first active player to have an award named after him.

Beginning in 1969, Brock produced six consecutive seasons with 190 hits or better. He was named NL Player of the Month for the first of three times in his career in May 1971 with a .405 batting average and 8 stolen bases. In August 1973, he broke a record set by Ty Cobb when he stole his 50th base of the season, marking the ninth time he had stolen 50 or more bases in a season. Brock won his second NL Player of the Month Award in August 1974, marking one of only four times the award was given to a player who slugged below .500.

In 1972, Brock improved on Maury Wills’ method by, instead of trying to maximize lead off distance, focusing on starting with a little momentum. “Brock pioneered the rolling start,” states a later Sports Illustrated article, which also maintains that base-stealing tends to be over-rated as a factor in team success.

On September 10, 1974, Brock tied Wills’ single-season stolen bases mark of 104 with a first-inning steal of second base, and then captured sole possession of the record with another swipe of second in the seventh inning. He ended the season with a new major league single-season record of 118 stolen bases. Brock finished second to Steve Garvey in the balloting for the 1974 National League Most Valuable Player Award.

In a game against the San Diego Padres on August 29, 1977, at San Diego Stadium, Brock became the all-time major league stolen base leader when he broke Ty Cobb’s career record of 892 stolen bases. The record had been one of the most durable in baseball history and like Babe Ruth’s record of 714 career home runs, had been considered unbreakable by some observers. Brock held this record until May 31, 1991, when it was broken by Rickey Henderson of the Oakland Athletics, who would go on to steal a total of 1,406.

Brock fell into a hitting slump early in the 1978 season and lost the left fielder’s job. However, he fought back during spring training in 1979 with a .345 batting average to regain his starting job. Brock was named Player of the Month for the month of May 1979, when he produced a .433 batting average.

On August 13, 1979, Brock became the fourteenth player in Major League Baseball history to reach the 3,000 hits plateau against the team that traded him, the Chicago Cubs. Approximately one month later, Carl Yastrzemski reached the same plateau and was promptly invited to the White House by Massachusetts native and Speaker of the House Tip O’Neill. Brock was reported to have felt slighted that he hadn’t received a similar invitation. Brock originally stated that he wouldn’t go to the White House even if he was invited. However, after consideration, he decided that forgiveness was the best course and accepted a belated invitation to meet with the President. Brock retired at the end of the season, having posted a .304 batting average in his last season at the age of 40. At the end of the season, he was named the National League Comeback Player of the Year — the first player to be so named in his final Major League season.

In October 1979, Brock was named the National League’s Comeback Player of the Year. In December 1979, he was named as the recipient of the Hutch Award, given to the player who best exemplifies the fighting spirit and competitive desire of Fred Hutchinson. Also on Sunday September 9, 1979, the St. Louis Cardinals retired Brock’s jersey number 20, an honor that had previously been bestowed upon only three other Cardinals players; Stan Musial, Dizzy Dean, and Bob Gibson. In 1983 he was inducted into the Louisiana Sports Hall of Fame. In 2014, the Cardinals announced Brock among 22 former players and personnel to be inducted into the St. Louis Cardinals Hall of Fame Museum for its inaugural class of 2014.

After retiring from baseball, Brock prospered as a businessman, especially as a florist in the St. Louis, Missouri area. He briefly worked as a color analyst for Monday Night Baseball on ABC in 1980, and for Chicago White Sox telecasts the following year. Brock regularly appeared at Cardinals games. When he stepped onto the field he was always greeted by a loud, low-pitched cheer of “Loooouuuuuuuuuuuu”. He also lent his name to a unique rainhat, shaped like a miniature umbrella, and to be worn at games during showers in lieu of retreating to the concourse. The product was called the “Brockabrella”.

Brock held the single-season stolen base record with 118 until it was broken by Rickey Henderson with 130 in 1982. He also held the major league record for a career stolen bases with 938 until it was also broken by Henderson in 1991. He led the National League in stolen bases for a record eight times and also had a record 12 consecutive seasons with 50 or more stolen bases. Brock is still the National League’s leader in career stolen bases.

Brock was inducted into the Baseball Hall of Fame in 1985, his first year of eligibility. He was inducted into the Missouri Sports Hall of Fame in 1992. Brock was inducted into the St. Louis Walk of Fame in May 1994 and, in 1995 he was inducted into the Arkansas Sports Hall of Fame. In 1999, he was ranked Number 58 on The Sporting News’ list of the 100 Greatest Baseball Players, and was nominated as a finalist for the Major League Baseball All-Century Team.

Brock and his wife, Jackie, were both ordained ministers serving at Abundant Life Fellowship Church in St. Louis, and he was a director on the board of YTB International. Brock’s speed was referenced in the song “Check the Rhime” by the pioneering “jazz rap” hip-hop ensemble A Tribe Called Quest. On December 5, 2006 he was recognized for his accomplishments on and off of the field when he received the Bobby Bragan Youth Foundation Lifetime Achievement Award. Brock was the father of former University of Southern California Trojan and National Football League player Lou Brock Jr.

Brock’s left leg was amputated below the knee in October 2015 because of an infection related to a diabetic condition.

Brock announced on April 13, 2017, that he was diagnosed with multiple myeloma, a blood cancer that starts in the bone marrow’s plasma cells. On July 28, 2017, Brock and his wife said they had received word from Mercy Hospital’s doctors that, according to their blood tests, the cancerous cells were gone. Brock said the cancer had been declining for some time. “We got reports that it was 25% gone, then 50%, then 75% gone,” he said. “The doctors were absolute. [Cancer] is not there.”