He played 10 seasons in the National Hockey League for the New Jersey Devils, Toronto Maple Leafs, and Columbus Blue Jackets.

[4] Following his junior ice hockey career, Clarkson went undrafted and was signed as a free agent by the New Jersey Devils on August 12, 2005.

[13] As the 2012–13 NHL lockout began, Clarkson signed with Austrian team EC Red Bull Salzburg to begin the 2012–13 season.

[14] Once the NHL lock-out was settled, he returned to the Devils and did well offensively, scoring 15 goals[15] though New Jersey failed to the make the playoffs.

[16] An unrestricted free agent, Clarkson did not re-sign with the Devils during the off-season, instead signing a seven-year, $36.75 million contract with the Toronto Maple Leafs on July 5, 2013.

[20] Clarkson was suspended for a second time that season, sitting out two games after hitting Vladimir Sobotka of the St. Louis Blues in the head.

[22][23] In the midst of his second season with the Maple Leafs, unable to establish a level of play to match his contract and plagued by injuries, Clarkson was traded by Toronto to the Columbus Blue Jackets in exchange for Nathan Horton on February 26, 2015.

[24] Healthy scratches and injuries would hold Clarkson to only 26 games with the Blue Jackets over the next year and a half, registering only 4 points.

As training camp for the 2016–17 season approached, it was announced that Clarkson had failed a physical and would not be invited to practice with the Blue Jackets.

[29] On July 23, 2019, Clarkson, along with a 2020 fourth-round pick, was traded back to the Maple Leafs in exchange for goaltender Garret Sparks.