Sewell became an immediate starter during his freshman year for the Ducks in 2018, starting seven games but missing six due to a high ankle sprain.[10][11] He returned in 2019 and won the Morris Trophy and Outland Trophy.[12][13] In addition, he and former Alabama quarterback Tua Tagovailoa were selected as co-recipients of the 2019 Polynesian College Football Player of the Year award.[14] Sewell opted out of the 2020 season due to the COVID-19 pandemic and declared for the 2021 NFL draft.[15]
Regarded as one of the best overall prospects in the 2021 NFL draft, Sewell was selected seventh overall by the Detroit Lions.[18] He tested positive for COVID-19 in May 2021 and had to sit out of minicamp.[19] He signed his four-year rookie contract, worth $24.1 million, the same month.[20] As a rookie, he appeared and started in 16 games, only being inactive for the regular season finale.[21] He was named to the 2021 Pro Football Writers Association All-Rookie Team.[22]
In Week 14 of the 2022 season, Sewell had a nine-yard reception late in the fourth quarter to give the Lions a crucial first down in the 34–23 victory over the Minnesota Vikings.[23] In the 2022 season, he started all 17 games and was named a Pro Bowl alternate.[24][25] In 2023, Sewell started all 17 games and was selected to his second Pro Bowl and first First-team All-Pro, and played in the NFC Championship with the Lions, where they lost 34–31.[26][27] He was ranked 22nd by his fellow players on the NFL Top 100 Players of 2024.[28]
On April 24, 2024, Sewell signed a four-year, $112 million contract extension with the Lions, keeping him under contract through the 2029 season.[29] He started all 17 games in the 2024 season.[30] He earned first team All-Pro and Pro Bowl honors for the 2024 season.[31][32] He was ranked 13th by his fellow players on the NFL Top 100 Players of 2025.[33]
Sewell started in and appeared in 16 games in the 2025 season.[34] He earned Pro Bowl and first team All-Pro honors for the 2025 season.[35][36]
↑Vondersmith, Jason (December 31, 2019). "Sewell's star shines brightly". Portland Tribune. Pamplin Media Group. Archived from the original on October 1, 2020. Retrieved April 3, 2021.