Dorsett played at Miami from 2011 to 2014. As a true freshman in 2011, he appeared in 12 games. He recorded 14 receptions for 147 yards and a touchdown. As a sophomore in 2012, he played in 12 games with 10 starts and led the team with 58 receptions for 842 yards and four touchdowns. As a junior in 2013, Dorsett played in only eight games due to a knee injury. He finished the year with 13 receptions for 272 yards and two touchdowns. Dorsett started all 13 games his senior season in 2014, recording 36 receptions for 871 yards and 10 touchdowns.

Dorsett was drafted 29th overall by the Indianapolis Colts in the 2015 NFL Draft. The drafting of Dorsett was a surprise to many analysts and fans, considering Indianapolis already had depth at the wide receiver position, including the recently signed Andre Johnson and Duron Carter, and the selection reportedly upset several Colts players, who thought the team should have instead focused on a defensive player.

Dorsett signed a four-year contract with the Colts on May 27, 2015. During Week 3 against the Tennessee Titans, he caught his first NFL touchdown on a 35-yard reception from Andrew Luck. He finished the game with two receptions for 43 yards and a touchdown. Dorsett finished his rookie season with 18 receptions for 225 yards and a touchdown in 11 games and zero starts.

In the 2016 season-opening loss to the Detroit Lions, Dorsett caught four passes for 94 yards in the 39-35 loss. Three weeks later, he caught a career-long 64-yard touchdown in a 30-27 loss to the Jacksonville Jaguars. During Week 15 against the Minnesota Vikings, he caught his second and final touchdown of the season on a 50-yard pass from Andrew Luck. Overall, Dorsett finished the 2016 season with 33 receptions for 528 yards and two touchdowns in 15 games and seven starts.

On September 2, 2017, Dorsett was traded to the New England Patriots for quarterback Jacoby Brissett.On September 7, Dorsett made his Patriots debut in the 42–27 loss to the Kansas City Chiefs. Dorsett finished his first season with the Patriots with 12 receptions for 194 yards. Despite his limited playing time, he caught a 31-yard pass on a flea-flicker from Tom Brady in the AFC Championship Game against the Jacksonville Jaguars as the Patriots won by a score of 24-20, advancing to Super Bowl LII. In the Super Bowl, Dorsett recorded one catch for 19 yards as the Patriots lost to the Philadelphia Eagles by a score of 41-33.

On May 2, 2018, the Patriots declined the fifth-year option on Dorsett’s contract, making him a free agent in 2019.

On March 13, 2019, Dorsett re-signed with the Patriots on a one-year contract.

On March 30, 2020, Dorsett signed a one-year contract with the Seattle Seahawks. After not playing in the team’s first two games while nursing a foot injury, Dorsett was placed on injured reserve on September 22, 2020.