He played college football for the UCLA Bruins, earning consensus All-American honors.

[3] As a senior, Lewis was named as a Parade magazine high school All-American and was considered a top prospect by all major recruiting services.

[4] Lewis attended the University of California, Los Angeles (UCLA), and played college football for the Bruins from 2002 to 2005.

As a senior in 2005, Lewis was a first-team All-Pacific-10 selection, a consensus All-American,[6] and won the John Mackey Award, given annually to the top tight end in college football.

[12] He played college football at UCLA with running back Maurice Jones-Drew, who was also selected on the first day by the Jaguars.

[14] He scored his first professional touchdown on a one-yard reception from David Garrard in Week 12 against the Buffalo Bills.

[19] In the 2010 season, Lewis matched the Jaguars single-season touchdown receptions record with a total of 10 and was selected to his first Pro Bowl.

[28] Lewis continued his constant production in the 2015 season with 16 receptions for 226 receiving yards in 16 games, all starts.

[34] In the AFC Championship loss to the New England Patriots, Lewis recorded his first postseason touchdown on a four-yard reception from Blake Bortles.

[41][42] Lewis caught his first touchdown as a Packer, a one-yard reception from Aaron Rodgers, on December 1, 2019, during a Week 13 victory over the New York Giants.

[57] He played in all 17 games with four starts primarily as a blocker, but did have a one-yard touchdown catch in a 27–16 win over the Cardinals.

[58] Lewis initially entered free agency but re-signed with the Bears on a one-year contract on June 10, 2024.

[61] Lewis has been active in his hometown of Long Beach, California, holding football camps that combine sports development with academics.