Regarded as a five-star recruit by Rivals.com, McCoy was ranked as the No. 1 defensive tackle prospect in his class. At No. 4 in the overall ranking he was the highest ranked defensive tackle since Haloti Ngata (No. 2) in 2002. Recruited by virtually every major school in the country, McCoy took official visits to Notre Dame, Southern California, Virginia Tech, Louisiana State, and Miami (FL), before committing to his home-state Sooners on National Signing Day.

McCoy was born in Oklahoma City to Gerald McCoy, Sr. and Patricia McCoy. He attended Southeast High School in Oklahoma City, where he played for the Southeast Spartans high school football team and competed in track. After notching 83 tackles, including 23 tackles for loss and 20 sacks, he was named All-area, all-state, and all-metro as a junior in 2004. As a senior, he logged 82 tackles, 20 sacks and recovered nine fumbles. McCoy received numerous awards including 2005 National Defensive Player of the Year by USA Today. Following his senior season, McCoy played in the 2006 U.S. Army All-American Bowl.

After being redshirted for the 2006 season, the young McCoy faced high expectations. In 2007, the Big 12 named McCoy the Defensive Freshman of the Year. He finished the 2007 season with 19 tackles, 6.5 tackles for loss, and two sacks while starting and playing in 13 games.

Despite having been considered one of the top prospects for the 2009 NFL Draft, McCoy chose to return to Oklahoma for his junior season. Rivals.com ranked him as the No. 2 defensive tackle in college football in 2009. McCoy finished the season playing in 15 games making 35 tackles (15.5 for losses) six sacks, two passes broken up, one forced fumble, and one fumble recovery. He was voted First-team All-American by the Walter Camp Foundation. McCoy also became the 37th Sooner player to earn All-America honors in more than one season. He was named to All-America teams by The Sporting News and Sports Illustrated after the 2008 season. On November 10, McCoy was named one of four finalists for the 2009 Lombardi Award. McCoy was the only non-senior on a list that also included Terrence Cody, Jerry Hughes, and Ndamukong Suh.

McCoy made his NFL debut against the Cleveland Browns on September 12, 2010. The Buccaneers won the game 17-14, thanks in large part to a great defensive performance that saw McCoy make three tackles while forcing a fumble. McCoy also became just the fifth defensive rookie to start for the Buccaneers on opening day since 1995 when Warren Sapp played against the Philadelphia Eagles in a 21-6 victory. McCoy recorded his first NFL sack against the San Francisco 49ers on November 21, 2010. In the game, the Bucs shut out the Niners 21-0 for their first win in Candlestick Park since 1980. His first multi-sack game came a week later, on November 28, 2010 when he sacked quarterback Joe Flacco of the Baltimore Ravens twice. The Buccaneers ended up losing that game 17 to 10 despite a strong defensive performance. On December 12, 2010, McCoy suffered a torn left biceps, causing the team to place him on IR two days later.

McCoy finished 2010 tied for third on the Buccaneers with 3.0 sacks, tied for fourth on the team with 6.0 tackles for loss and ranked second with 17 quarterback pressures during his rookie season, despite missing the final three games.

McCoy was placed on injured reserve on November 7, 2011 after tearing his right biceps during the opening quarter of a 27–16 loss to New Orleans that dropped the Bucs (4–4) into third place in the NFC South. He had just returned to the lineup after sitting out the previous two games because on an ankle injury.

McCoy bounced back in 2012, having a significant impact on the Bucs’ top-ranked rushing defense and earning his first Pro Bowl berth in his first season un-marred by injury.

McCoy majored in human relations at the University of Oklahoma. In May 2012, McCoy was presented with the 2012 Pop Warner Little Scholars ‘Inspiration to Youth’ Award at Pop Warner’s annual All-American Scholastic Banquet in Orlando, Florida. In September 2012, McCoy helped present a $100,000 check to build Tampa Bay Buccaneers Field in Clearwater’s North Greenwood community, where McCoy and teammates also led local youths through football drills. Gerald McCoy is married to Ebony McCoy, and the couple have five children. McCoy also appeared, along with J. J. Watt and NaVorro Bowman, in The League, a TV series centered around a fantasy football league, for Episode 2 of Season 5.

McCoy began the 2013 season in good form, registering 2 sacks and a fumble recovery by Week 4. McCoy continued his strong season with a big game against the Miami Dolphins in Week 10. He recorded 5 tackles including 2 for a loss, and also sacked Miami Quarterback Ryan Tannehill. McCoy enjoyed the most productive day of his career in Week 11 of the 2013 season. Registering 6 tackles, 3 sacks and a pass deflection at home against the Atlanta Falcons, tying a franchise single-game sack record for a defensive tackle with Warren Sapp and Brad Culpepper. McCoy was voted to his second consecutive Pro Bowl in 2013. He finished the season with 50 Total Tackles, 9 Sacks, 8 Tackles for a Loss, 4 Pass Deflections and a Fumble Recovery. He was ranked by Pro Football Focus as the NFL’s Best Defensive Tackle for the 2013 NFL Season. McCoy was named first-team All-Pro by the associated press along with teammate Lavonte David.

McCoy and the Bucs entered the 2014 season with a new head coach, Lovie Smith. He is McCoy’s third coach in 5 NFL seasons. After continuing his strong play and being a stand out leader of the Bucs defense McCoy and Tampa Bay were working on a new deal. On October 25, 2014, McCoy signed a 7-year extension worth $98 million, and $51.5 million guaranteed. At the time, it was the biggest contract ever for a defensive tackle. During week 15 against the Carolina Panthers McCoy injured his knee and was placed on Injured reserve the following Tuesday ending his 2014 season with 35 combined tackles, 28 solo tackles, 8.5 sacks, and 1 forced fumble. Despite his injury he was selected to his third consecutive Pro Bowl.

In 2016, McCoy was named to his fifth-straight Pro Bowl and was named second-team All-Pro. He was also ranked 52nd on the NFL Top 100 Players of 2017.

On December 19, 2017, McCoy was named to his sixth straight Pro Bowl.

On May 20, 2019, McCoy was released by the Buccaneers after spending nine seasons with the team.

On June 3, 2019, McCoy signed with the Carolina Panthers. In week 6 against the Tampa Bay Buccaneers, McCoy sacked former teammate Jameis Winston 2.5 times in the 37-26 win.

On March 31, 2020, McCoy signed a three-year contract with the Dallas Cowboys. After suffering a ruptured quadriceps injury in practice, he was released by the Cowboys on August 18, 2020, through an injury waiver clause in his contract.