He first competed professionally in the 1999 Arnold Classic, Night of Champions, and Mr. Olympia contests, placing 7th, 3rd, and 9th, respectively.

On September 27, 2008, he defeated reigning champion Jay Cutler to become the 12th man to win the title and only the second man since Ronnie Coleman to win both Mr. Olympia and Arnold Classic title in the same calendar year.

Jackson has won the Mr. Olympia Men's Open title once, sharing this distinction with Chris Dickerson (1982), Samir Bannout (1983), Shawn Rhoden (2018), Brandon Curry (2019), Hadi Choopan (2022), and Derek Lunsford (2023).

Jackson has been featured in many fitness and bodybuilding articles, including being pictured on the cover of Muscular Development and Flex magazine.

In 2009, following his win at the 2008 Mr. Olympia, Jackson created his own bodybuilding competition, The Dexter Classic.