He played college football at Ole Miss and was selected by the Bills in the third round of the 2019 NFL draft.

[5] After his junior season in 2018, he decided to forgo his senior year and enter the 2019 NFL draft.

[11] On September 22, 2019, Knox caught his first NFL touchdown from Josh Allen against the Cincinnati Bengals in Week 3.

[16] In Buffalo's Wild Card Round victory over the Indianapolis Colts, Knox caught two passes for five yards, including a two-yard touchdown from Josh Allen in the first quarter of the Bills' eventual 27–24 victory.

[17] In the AFC Championship against the Kansas City Chiefs, Knox recorded six catches for 42 yards and a touchdown during the 38–24 loss.

[21] On September 7, 2022, the Bills signed Knox to a four-year $53.6 million extension, making him one of the top paid tight ends in the league.

[24] He scored a receiving touchdown in the Bills' 34–31 Wild Card Round victory over the Miami Dolphins.