Newsome was a star at the University of Alabama and played for the Cleveland Browns in the NFL. He made the College Football All-America Team in 1977 and assisted the Crimson Tide to a 42-5 overall record during his four seasons. In total, Newsome amassed 102 receptions for 2,070 receiving yards. His 20.3 average yards per catch was a conference record. In 1994, Newsome was enshrined in the College Football Hall of Fame.

After graduating college, he was the Browns' first-round draft pick in 1978. He was All-Pro and was named to three Pro Bowls. He ultimately caught 662 passes for 7,980 yards and 47 touchdowns, and had a catch in every game for 150 consecutive games. He recorded career-best 89 catches in 1983, and recorded it again in 1984. He retired in 1990 as the NFL's all-time leading tight-end receiver. He was elected to the Pro Football Hall of Fame in 1999. Newsome made NFL history on November 22, 2002, when he became the first ever African-American general manager in the league.

Since retiring, Newsome has worked in various positions for the Baltimore Ravens, including General Manager.