He played in Major League Baseball (MLB) for the Tampa Bay Rays, Arizona Diamondbacks, Philadelphia Phillies, Baltimore Orioles, and Washington Nationals.

[7] On August 21, 2010, Hellickson was optioned to the High-A Charlotte Stone Crabs to work on moving to the bullpen.

[9] He was named the Rays third starter for the 2012 season and pitched 82⁄3 shutout innings against the New York Yankees on April 8, 2012.

[11] He was named co-winner with Jake Peavy, then with the Chicago White Sox, of the American League Rawlings Gold Glove for 2012.

On November 14, 2014, the Rays traded Hellickson to the Arizona Diamondbacks for Andrew Velazquez and Justin Williams.

On November 14, 2015, Hellickson was traded to the Philadelphia Phillies for minor league pitcher Sam McWilliams.

[19] On July 28, 2017, the Phillies traded Hellickson to the Baltimore Orioles for Hyun-soo Kim and Garrett Cleavinger.

[20] In his first start as an Oriole, Hellickson threw seven shutout innings against the Royals, striking out three batters while earning the win in a 6–0 victory.

[24] He earned his first Nationals win on May 8, 2018, at PETCO Park, taking a perfect game bid into the seventh inning and allowing no runs in the two-hit outing, striking out eight San Diego Padres in the process.

The Nationals finished the 2019 year with a 93–69 record, clinching a wild card spot, and eventually went on to win the 2019 World Series over the Houston Astros, their first championship in franchise history.

[28] Hellickson retired from baseball on February 14, 2020, after experiencing a shoulder setback prior to spring training.