Lewis played at Hialeah Miami Lakes High School under coach Jerry Hughes. As a senior, he was evaluated as the nation's 10th-best dual-threat quarterback and 65th-best quarterback overall. He led his team to the state playoffs that year, passing for 12 touchdowns and only three interceptions.
Lewis played college football for the Duke Blue Devils. While at Duke he set school records for career passing touchdowns and career passing yards. He also set Duke's school record for most consecutive pass attempts without an interception, 206. During his four years as a starting quarterback, he threw for 10,065 yards, 67 touchdowns and 40 interceptions, and ran for 9 touchdowns.
During his senior season Lewis was a finalist for the Davey O'Brien Award, presented to the nation's top quarterback.
The Cleveland Browns claimed him off of waivers on September 4. Lewis was later waived by the Browns on October 11, 2012. He was signed to the practice squad on October 13, 2012. He was again added to the Cleveland Browns active roster December 24, 2012 after injuries to Brandon Weeden and Colt McCoy. He made his first career start when the Browns took on the Pittsburgh Steelers on December 30, 2012 and completed 22 of 32 passes for 204 yards with one touchdown and one interception. Notwithstanding Lewis' performance, the Browns lost 24-10. This performance is particularly noteworthy due to his strong performance against the first ranked defense in the NFL during the 2012 season.
On August 25, 2013, the Buffalo Bills traded linebacker Chris White for Lewis, due to the mounting quarterback injuries for the Bills. He was released on August 31, 2013 and signed to the practice squad September 1. On October 7, 2013, coach Doug Marrone announced on WGR Radio 550 that Lewis was promoted to the active roster from the practice squad after an injury to EJ Manuel and started week 6 against the Cincinnati Bengals over undrafted rookie Jeff Tuel where he had two passing touchdowns and one rushing touchdown. The Bills lost the game in overtime by a score of 27-24.A week later on October 20, 2013, Lewis earned his first career victory against the Miami Dolphins by a score of 23-21. He then lead the Bills to their second victory as the starting quarterback in a shut out victory against the division rival Miami Dolphins in Week 16 to the score of 19-0. The loss would be a major factor for the Dolphins in not making the playoffs since they needed to win one of their final two games for a wildcard spot - they ended up losing both games. Lewis finished the season with a 2-3 record as the Bills starting quarterback. On August 26, 2014, he was released from the Bills.
Lewis signed with the Houston Texans on November 24, 2014, after starting quarterback Ryan Mallett suffered an season ending injury, but was then released during the off season leading up to the 2015 season.