After having a productive rookie season cut short by injury, Watson guided the Texans to consecutive division titles in 2018 and 2019 and led the league in passing yards in 2020.

[5] Disagreements with the Texans' front office, and multiple sexual-misconduct lawsuits, kept Watson out for the entire 2021 season and eventually led to a trade to the Browns in 2022.

[15] Watson entered his true freshman season as the backup to starter Cole Stoudt, but still received extensive playing time.

[17][18] In Watson's first career start against the North Carolina Tar Heels, he set a school record with six touchdown passes and threw for 435 yards en route to a 50–35 victory.

[29][30] With the win, the Tigers advanced to the 2016 College Football Playoff National Championship game against the #2 Alabama Crimson Tide, but Clemson lost 45–40.

[36][37] Watson started his junior season positively with 248 passing yards, one touchdown, and one interception in a narrow 19–13 victory over the Auburn Tigers.

[44] For the second consecutive year, Watson was named one of the five Heisman Trophy candidates, along with Michigan's Jabrill Peppers, Oklahoma's Baker Mayfield and Dede Westbrook and Louisville's Lamar Jackson.

[49] On November 8, 2016, Watson, along with three other Clemson players, Wayne Gallman, Artavis Scott and Mike Williams,[50] declared for the NFL draft.

Houston had already traded quarterback Brock Osweiler to Cleveland for draft picks earlier that year as part of what was widely considered the NFL's first major "salary dump."

Watson was the third quarterback taken in the draft behind Mitchell Trubisky, who went second overall to the Chicago Bears, and Patrick Mahomes, who went tenth overall to the Kansas City Chiefs.

[82] After suffering broken ribs and a partially collapsed lung, Watson took a 12-hour bus ride from Houston to Jacksonville for a Week 7 game against the Jaguars rather than flying because of fears about the effects of air pressure on his chest.

[104] In the Wild Card Round against the Buffalo Bills, Watson led the Texans back from a 16–0 deficit to win 22–19 in overtime, his first NFL playoff victory, despite being sacked seven times.

He sealed the game by spinning out of a potential sack by two Bills defenders and finding Taiwan Jones, who ran to the Buffalo 10-yard line to set up the game-winning field goal in overtime.

[115] With his Week 12 performance, Watson briefly became the NFL's all-time regular-season career passer-rating leader before being surpassed five days later by Patrick Mahomes.

[116] Watson was fined $7,500 by the Texans in December 2020 for violating the league's COVID-19 protocols after he and several teammates gathered at the opening of his new restaurant without wearing face masks.

Despite the off-field controversies and Watson's situation with the team, he participated in OTA activities and training camp, albeit on a limited basis.

[124] Watson was named to the Texans' 53-man roster to start the season along with free-agent signing Tyrod Taylor and rookie Davis Mills.

[134][135] On August 18, 2022, after the NFL and the NFLPA reached a settlement, Watson was suspended for the first 11 games of the 2022 regular season and was fined $5 million.

In his first game in 700 days, Watson posted the worst passer rating of his NFL career at 53.4, throwing for 131 yards and one interception in the 27–14 win.

[140] In week 10 against the Baltimore Ravens, Watson suffered a displaced fracture to the glenoid in his right shoulder during the first half, but he was able to finish the game.

Three days later, on November 15, the Browns announced that Watson would undergo season-ending surgery to repair a broken bone in his throwing shoulder.

[146] On October 20, during the Browns' Week 7 matchup against the Cincinnati Bengals, Watson was carted off the field after suffering a non-contact leg injury.

[150] On January 9, 2025, Watson underwent surgery after he suffered a re-rupture to his right Achilles tendon, potentially keeping him out for the entire 2025 season.

[153] On March 18, a third civil lawsuit was filed against Watson, alleging that he had forced a massage therapist to perform oral sex on him before she blacked out in an office building in December 2020.

Buzbee requested that the Houston Police Department and the Harris County, Texas, district attorney investigate the situation and pursue criminal charges against Watson.

The traveling massage therapist alleged that when she arrived at the address that Watson had provided, he led her to a room and "locked the doors behind him".

[162] Ashley Solis, the first of the women to identify herself, claimed that during a massage appointment at her home, Watson exposed himself and touched her hand with his erect penis before she ended the session and asked him to leave.

[169] On March 11, 2022, a grand jury declined to indict Watson on criminal charges related to "harassment and sexual misconduct".

[171] As a result of these accusations, the NFL announced on August 18, 2022, that Watson would be suspended for 11 games, pay a record $5 million fine, undergo evaluation by behavioral experts, and complete a treatment program.

[183] In 2017, Watson donated his first NFL game check of approximately $27,000 to three NRG Stadium cafeteria employees affected by Hurricane Harvey.