Pittsburgh Steelers Claypool was selected by the
Pittsburgh Steelers in the second round, 49th overall, in the
2020 NFL draft as the team's first selection. Although eligible as a Canadian and rated as the No. 2 prospect, Claypool went undrafted in the
2020 CFL draft. On July 22, 2020, the Steelers signed Claypool to a four-year, $6.61 million rookie contract that includes $3.28 million guaranteed and a signing bonus $2.37 million. On September 20, during Week 2 against the
Denver Broncos, Claypool finished with three receptions for 88 receiving yards, including an 84-yard touchdown, as the Steelers won 26–21. In Week 5, against the
Philadelphia Eagles, Claypool finished with 110 receiving yards and four total touchdowns (three receiving & one rushing), both career highs, as the Steelers won 38–29. With his Week 5 effort, Claypool became the first Steelers rookie in franchise history to score four touchdowns in a game, and the first Steeler since
Roy Jefferson in 1968 to do so. His performance helped the team start out with a 4–0 record for the first time since 1979. On October 14, Claypool was named the AFC Offensive Player of the Week for his performance in Week 5. In Week 10, against the
Cincinnati Bengals, he had four receptions for 56 receiving yards and two receiving touchdowns in their 36–10 victory. Claypool had a successful rookie year, catching 62 passes for 873 yards and 9 touchdowns, in addition to two rushing touchdowns. He was named to the PFWA All-Rookie Team. In the Wild Card round of the playoffs against the
Cleveland Browns, Claypool recorded 5 catches for 59 yards and two touchdowns during the 48–37 loss. The following season, during a game against the
Minnesota Vikings, Claypool, who had already been pulled from the game earlier for poking Vikings cornerback
Bashaud Breeland in the face, received criticism after celebrating a first down reception while the Steelers were trailing 36–28 with just 30 seconds left in the game. The celebration, which was noted by
CBS Sports to take "at least 5 seconds" off the clock, wound up being costly as the Steelers could not score in time and lost the game. Overall, Claypool played in 15 games in 2021, starting 13, and posted similar catch and yardage totals compared to his rookie season, though he only caught two touchdowns.
Chicago Bears Claypool was traded to the
Chicago Bears on November 1, 2022, in exchange for their second-round pick (32nd overall; later used to select
Joey Porter Jr.) in the
2023 NFL draft. He was intensely criticized for a low-effort performance in the Bears' 2023 season opener against the
Green Bay Packers. It was reported on September 17 that Claypool had apologized for this to his teammates and coaches. By week 4, Claypool expressed frustration with the Bears and stated that he did not believe the coaching staff put him in a position to succeed. The Bears deactivated him before their week 4 matchup against the Broncos, and activated
Equanimeous St. Brown in his place. Claypool had been told by the team to stay home during the Denver game, and was later told not to return to their facility while they searched for a trade partner the following week. The team had instructed him to remain at home the following week as well, while they won in a
Thursday Night Football road game (their first win since October 24, 2022) against the
Washington Commanders. As a Bear, he appeared in ten games, recording 191 receiving yards and one touchdown on 18 receptions.
Miami Dolphins On October 6, 2023, the Bears traded Claypool and a seventh-round selection in the
2025 NFL draft to the
Miami Dolphins in exchange for a sixth-round selection in the 2025 NFL Draft. In Week 8 vs. the
New England Patriots, Claypool caught 1 pass for 15 yards, his first reception with the Dolphins.
Buffalo Bills On May 3, 2024, Claypool signed a one-year contract with the
Buffalo Bills. On August 12, Claypool was placed on injured reserve after tearing a ligament and tendon in his second toe. He was released with an injury settlement on August 15. In July 2025, Claypool announced he was attempting to return to the NFL. ==Career statistics==