Gonzalez was ranked as one of the top tight ends in the 1997 NFL Draft and was considered a top 15 selection. The Chiefs traded up from the 18th to the 13th selection with the Tennessee Oilers to draft Gonzalez.

Gonzalez began his career in the 1997 season. He finished his rookie season with 33 receptions, two touchdowns, and a blocked punt on special teams, helping the Chiefs to finish with the best record in the American Football Conference (AFC). He was named to the NFL All-Rookie Team for the 1997 season. In the 1998 season, Gonzalez saw dramatic improvements with 59 receptions for 621 yards, and also caught two touchdown passes for the second consecutive year.

The 1999 season saw Gonzalez again improving when he caught 76 passes for 849 yards and a career-high 11 touchdown receptions, earning his first Pro Bowl selection. In addition, he was named as a First Team All-Pro. In the 2000 season, he had 93 receptions for 1,203 receiving yards and nine receiving touchdowns. He was named to the Pro Bowl and as a First Team All-Pro for the 2000 season. In the 2001 season, he had 73 receptions for 917 receiving yards and six receiving touchdowns while earning his third career First Team All-Pro honor and Pro Bowl nomination. On November 4, against the San Diego Chargers, he threw his first professional pass, which went for 40 yards. In the 2002 season, he had 63 receptions for 773 receiving yards and seven receiving touchdowns to go along with another Pro Bowl nod. Among the highlights from that season was a 48–30 victory over the Miami Dolphins where he had seven receptions for 140 receiving yards and a career-high three touchdowns. From 2003 to 2006, Gonzalez was the most productive tight end in the NFL. In the 2003 season, he had 71 receptions for 916 receiving yards and ten receiving touchdowns. For the fourth time in his career, he was named as a First Team All-Pro. He was named to his fifth consecutive Pro Bowl for the 2003 season. His best season statistically came in 2004, when he caught an NFL-record (for a tight end) 102 passes for 1,258 yards and seven touchdowns. In Week 17, he had a career-high 14 receptions for 144 yards against the San Diego Chargers. He earned a spot in the Pro Bowl for his historic season. Gonzalez’s single-season record of 102 receptions by a tight end stood for 8 years, until it was broken by Jason Witten during the 2012 season. In the 2005 season, he had 78 receptions for 905 receiving yards and two receiving touchdowns in another Pro Bowl season.

Starting late in 2006, Gonzalez began to close in on numerous team and league receiving records. He finished with 73 receptions for 900 receiving yards and five receiving touchdowns and earned his eight consecutive Pro Bowl nomination. In 2006, Gonzalez broke wide receiver Otis Taylor’s Chiefs team receiving yards and touchdowns mark, and also passed running back Priest Holmes for the team yards from scrimmage record.

In 2006, Gonzalez had a minor role in the TV Movie A.I. Assault, his first non-cameo acting job. He has also appeared in three episodes of NCIS as Special Agent Tony Francis. In the 2017 film XXX: Return of Xander Cage, he played Paul Donovan, his first feature film role as an actor. He’s also made cameo appearances as himself on other television series as well.

In 2007, Gonzalez continued his productivity in spite of the generally poor play of the Chiefs’ offense. Though the Chiefs finished at or near the bottom in most major offensive categories, Gonzalez led the Chiefs and all NFL tight ends in receptions (99) and receiving yards (1,172) while being named to his ninth straight Pro Bowl.

On October 14, 2007, Gonzalez broke the career touchdown reception record for tight ends previously held by Shannon Sharpe, as well as passing Ozzie Newsome for second in career receiving yards for a tight end. On December 23, 2007, Gonzalez recorded his third season with 1,000 receiving yards, tying him with Kellen Winslow, Todd Christensen, and Shannon Sharpe for most ever by a tight end, and on December 30, 2007, Gonzalez passed Shannon Sharpe for most receptions all time by a tight end.

In early 2007, Gonzalez suffered a bout of facial paralysis known as Bell’s Palsy. Gonzalez subsequently experimented with a vegan diet after reading The China Study, by Cornell professor and nutrition researcher T. Colin Campbell, but he and his nutritionist, Mitzi Dulan, ultimately decided that eating meat occasionally would be best for his performance. Gonzalez only eats organic fruits and vegetables, free-range chicken, grass fed beef (no more than 18 ounces a month), and fish.

Gonzalez had a commitment ceremony in July 2007 with his girlfriend, October, though the couple considers themselves married despite not being legally married. Gonzalez has three children with October, two daughters and a son. He has another son from a previous relationship with entertainment reporter Lauren Sánchez. He lives in Huntington Beach, California.

On July 3, 2008, while dining with his family at Capone’s Restaurant in Huntington Beach, Gonzalez noticed fellow diner Ken Hunter choking on a piece of meat at a nearby table, unable to breathe. Gonzalez successfully administered the Heimlich Maneuver to Hunter, saving his life. After the incident, it was revealed that Hunter was a fan of the San Diego Chargers, who are a rival team of the Chiefs in the AFC West.

He campaigned for Barack Obama in the 2008 Election, saying “this is the first time in my life that I’ve ever been political about anything.”

During the 2009 offseason, Gonzalez again approached Chiefs management about a possible trade. Unlike the previous Chiefs management, new Chiefs’ GM Scott Pioli told Gonzalez he would see what he could do.

In 2009, Gonzalez co-authored the book The All-Pro Diet. The book, co-written with Mitzi Dulan, the former nutritionist for the Chiefs, details his diet and workout routine and provides practical suggestions for others to follow the same path.

Later in 2009, Gonzalez co-founded All-Pro Science, a sports nutrition company that manufactures a complete line of protein shakes, vitamins and other supplements. The products in the APS line follow a similar philosophy to the one set forth in Gonzalez’s book, focusing on a balance of foods from all-natural sources.

Gonzalez was traded to the Atlanta Falcons in exchange for a second-round pick in the 2010 NFL Draft on April 23, 2009. In his first regular season game with Atlanta against the Miami Dolphins, Gonzalez caught a touchdown pass from Matt Ryan and became the 21st player, and the first tight end, in NFL history with 11,000 receiving yards. He finished the game leading the Falcons in receiving with five receptions for 73 yards and one touchdown, his 20-yard touchdown reception marking only the third time he scored in the opening game of the season. Although Gonzalez recorded 83 receptions for 867 yards and 6 touchdowns, his total statistics went down from the previous years in Kansas City, and Gonzalez was not invited to the Pro Bowl for the first time in 10 years. He was named to the Pro Football Hall of Fame All-Decade Team for the years 2000–2009.

In the 2010 regular season opener against the Pittsburgh Steelers, Gonzalez made his 1,000th career reception, making him the seventh player in NFL history to do so and the first tight end. Gonzalez had his best performance as a Falcon two weeks later against the defending Super Bowl champions New Orleans Saints, as caught eight catches for 110 yards and a touchdown to help lead Atlanta to an overtime victory. His play in 2010, helped him return to the Pro Bowl that year. The Falcons also finished 13-3 that season to earn the first-seed in the playoffs; in Gonzalez first playoff game in five years, the Falcons were defeated by the eventual Super Bowl champions Green Bay Packers.

During the NFL lockout in 2011, Gonzalez contemplated retiring rather than sitting out an entire season and waiting to play in 2012. After the lockout was eventually lifted by the league, Gonzalez was adamant he had at least three seasons left in him and was excited at the prospects of returning to the Falcons who are widely considered to be Super Bowl contenders. On the NFL Top 100 Players of 2011, he was ranked 46th by his fellow players.

In the 2011 season, Gonzalez finished with 80 receptions for 875 receiving yards and seven receiving touchdowns. He was named to the Pro Bowl and was ranked 53rd among his peers on the NFL Top 100 Players of 2012.

With Gonzalez’s contract set to expire following the conclusion of the 2011 season, he signed a 1-year $7 million contract extension with the Falcons on January 1, 2012 indicating his intent to return for at least one season. In the 2012 season opener, Gonzalez played in Arrowhead Stadium against the Chiefs for the first time in his career, which ended with a Falcons’ victory. Gonzalez caught his 100th career touchdown on November 11, 2012, in a week 10 game against the New Orleans Saints, becoming the only tight end in NFL history to catch 100 touchdown passes. Overall, he finished the 2012 season with 93 receptions for 930 receiving yard and eight receiving touchdowns to earn another First Team All-Pro honor and Pro Bowl nomination. On January 13, 2013, Gonzalez won the only playoff game of his career when the Falcons defeated the Seattle Seahawks 30-28. His fellow players ranked him 47th on the NFL Top 100 Players of 2013.

Throughout the 2012 season, he insisted on retiring. However, on March 12, 2013, on his Twitter page, he said, “I’m happy to say that after speaking with my family, I’m coming back.” Then, later that day, he posted,”The lure of being on such a great team and organization, along with unbelievable fan support was too good to pass up.”

On March 15, 2013, Gonzalez agreed to re-sign with the Falcons to a two-year, $14 million contract, despite his claim that he would be retiring after the 2013 season. With the retirement of Randy Moss, 37-year-old Gonzalez spent his last season as the NFL’s active leader in receiving yards. On September 29, against the New England Patriots, he had 12 receptions for a career-high 149 receiving yards and two touchdowns. Gonzalez played his final NFL game against the Carolina Panthers on December 29. He finished his final season with 83 receptions for 859 receiving yards and eight receiving touchdowns. He would later be named a second alternate for the Pro Bowl that season, and was added to the roster when San Francisco 49ers tight end Vernon Davis declined the invitation. It was his 14th and final Pro Bowl appearance, tying him with Bruce Matthews, Merlin Olsen, Peyton Manning and Tom Brady for the most selections for the game.

From 2013 to 2017, Tony worked with FitStar, a company that makes mobile fitness apps, helping people get in shape with customized workouts delivered via the iPhone, iPad and iPod touch. He appears in the FitStar Personal Trainer, leading users through personalized Sessions.

In March 2015, Gonzalez hosted You Can’t Lick Your Elbow on the National Geographic Channel, which ran for six episodes.

In 2015, Gonzalez and his older brother Chris, were profiled in the documentary, Play It Forward. The film premiered at the Opening Gala during the Tribeca Film Festival.

On May 10, 2017, Gonzalez was added to FOX’s pregame show.

Gonzalez competed against linebacker Ray Lewis in an episode of Spike’s Lip Sync Battle, which aired on February 2, 2017. He performed Digital Underground’s “The Humpty Dance” and Devo’s “Whip It”, but did not win.

Gonzalez is frequently considered the greatest tight end of all-time. During his career, he broke numerous NFL records for tight ends. Only two of his major records have been broken, most career touchdowns and most 1,000 yard seasons by a tight end. Additionally, he also owns several Chiefs team records and at the time of his retirement, he finished in the top 10 in many receiving categories for any position. He finished 5th in yards, 2nd in receptions, and 6th in touchdowns. On January 26, 2018, the Chiefs announced they would induct Gonzalez into the Chiefs Hall of Fame. He was inducted during halftime of a game during the 2018 season. In his first year of eligibility in 2019, Gonzalez was inducted into the Pro Football Hall of Fame.