He played college football for the UMass Minutemen,[1] and was selected by the Arizona Cardinals in the second round of the 2019 NFL draft.

[3] In his senior year of high school, Isabella won the state title in the 100-meter dash, beating fellow sprinter and future Cleveland Browns cornerback Denzel Ward in a close race.

[9][10] In 2018, he led the country in receiving yards per game (141.5) and was named to the 2018 College Football All-America Team.

[20] In Week 3 of the 2020 season, Isabella recorded four receptions for 47 receiving yards and two touchdowns in the 26–23 loss to the Detroit Lions.

[23] On December 31, 2022, Isabella was elevated to Baltimore's active roster for Week 17 versus the Pittsburgh Steelers.

On January 2, 2023, Isabella was put back on Baltimore's practice squad after a thigh injury versus Pittsburgh.

On January 14, 2023, Isabella was elevated to Baltimore's active roster again for their playoff game versus the Cincinnati Bengals.