Saint Preux played college football for the Tennessee Volunteers from 2001 to 2004. After redshirting in 2001, he played primarily as a reserve at both defensive end and linebacker. He earned varsity letters in 2002 and 2004, appearing in seventeen games during his college career. He graduated in 2004 with a degree in sociology, and began to train in kickboxing and grappling.
Saint Preux compiled an undefeated amateur MMA record of 5-0 before making his professional MMA debut at VFC 1 against Rodney Wallace, which he lost by decision. In his second MMA match, he suffered another decision loss. His next match came against Robert Turner which he won by a brutal head kick at XFC 7: School of Hard Knox. Saint Preux was a runner-up for Inside MMA's Submission of The Year for 2009 with a calf slicer against Ombey Mobley, but was beaten by Toby Imada's reverse triangle.
In June 2010, Saint Preux signed a multi-fight deal with Strikeforce. His debut match came against Chris Hawk at Strikeforce: Nashville, which he won due to TKO (punches) in the first round.
Saint Preux next fought Gegard Mousasi on December 17, 2011, at Strikeforce: Melendez vs. Masvidal. He lost the fight via unanimous decision.
Saint Preux fought T. J. Cook on August 18, 2012, at Strikeforce: Rousey vs. Kaufman. He won the fight via third round KO with a punch.
For his second bout with the promotion, Saint Preux faced Cody Donovan on August 17, 2013, at UFC Fight Night 26. He won the fight via knockout at 2:07 in the first round.
Saint Preux was expected to face Rafael Cavalcante on November 8, 2014 at UFC Fight Night 56. However, Cavalcante pulled out of the bout citing injury and was replaced by Francimar Barroso. However, on October 29, it was announced that Saint Preux would step up to replace an injured Jimi Manuwa in the main event against Maurício Rua. Despite being the underdog and fighting in Rua's home country of Brazil, Saint Preux won the fight via knockout just 34 seconds into the first round. Shogun's loss to Preux was the fastest defeat of his professional career. The win also earned Saint Preux his second Performance of the Night bonus award.
Saint Preux faced Glover Teixeira on August 8, 2015 at UFC Fight Night 73. He lost the back-and-forth fight by submission in the third round. Both participants were awarded Fight of the Night honors.
Saint Preux faced Jimi Manuwa on October 8, 2016 at UFC 204. He lost the fight via knockout in the second round.
Saint Preux stepped in to replace Patrick Cummins in a fight against Corey Anderson on November 4, 2017 at UFC 217. After winning the first round by landing the more effective strikes and rocking Anderson in the final seconds and losing the second round due to Anderson's wrestling, Saint Preux won the fight via a head kick knockout in the opening minute of the third round. This win earned him a $25,000 Performance of the Night bonus award.
Saint Preux is scheduled to face Tyson Pedro on June 23, 2018 at UFC Fight Night 132.