After redshirting his first year at Missouri in 2016, Okwuegbunam played in all 13 games in 2017 and recorded 29 receptions for 415 yards and 11 touchdowns.[4][5] He returned as Missouri's starter in 2018.[6][7] Following the 2019 season, Okwuegbunam decided to forgo his final year of eligibility and declared for the 2020 NFL draft.[8]
Okwuegbunam was selected by the Denver Broncos in the fourth round with the 118th overall pick in the 2020 NFL draft, reuniting with his former Missouri teammate, Drew Lock.[11] He made his NFL debut in Week 6 of the 2020 season against the New England Patriots. He had two receptions for 45 yards in the 18–12 victory.[12] He was placed on injured reserve on November 10, 2020, with a torn ACL.[13]
On October 9, 2021, Okwuegbunam was placed on injured reserve with a hamstring injury.[14] He was activated on October 30.[15]
In 2022, Okwuegbunam played in 8 games for Denver, catching 10 passes for 95 yards and one touchdown.[16]
Philadelphia Eagles
On August 29, 2023, Okwuegbunam was traded to the Philadelphia Eagles along with a 2025 seventh round pick for the Eagles’ 2024 sixth round pick.[17]
On February 23, 2024, Okwuegbunam signed a one-year contract extension with the Eagles.[18] He was placed on injured reserve on August 27.[19] He was released on November 5.[20]
Indianapolis Colts
On December 17, 2024, Okwuegbunam was signed to the Indianapolis Colts practice squad.[21]