Mitrione soon turned to mixed martial arts after
Jayson Werth, a professional baseball player for the
Washington Nationals, and close friend of Mitrione, invited Mitrione to fight in his inaugural promotion. Mitrione then relocated with his family to
Indianapolis, Indiana, where he began training with fighters
Chris Lytle and
Jake O'Brien.
The Ultimate Fighter Mitrione appeared on the tenth season of
The Ultimate Fighter. Later in an interview, Mitrione revealed that he joined the show only to promote his sports nutrition company. On the show, he was given the unofficial nickname "Meathead" by coach
Rashad Evans. After being picked second to last by Evans, Mitrione fought and defeated Scott Junk via majority decision (19–19, 20–18, and 20–18), moving him on to the quarter-finals. Following Mitrione's fight with Junk, Mitrione complained about migraines and dizziness, causing many of the cast members to feel that Mitrione may bow out of the competition to give
Kimbo Slice a second opportunity. Mitrione did fight and was eliminated by teammate
James McSweeney in the quarterfinals, losing via guillotine choke.
Ultimate Fighting Championship Mitrione made his professional MMA debut on December 5, 2009, at
The Ultimate Fighter: Heavyweights Finale defeating
Marcus Jones via KO early in the second round. Mitrione then faced another fellow
Ultimate Fighter alumnus
Kimbo Slice at
UFC 113 in Montreal. Mitrone chopped Slice down with leg kicks and eventually defeated Slice via technical knockout in the second round, taking his professional record to 2–0. Mitrione faced
Joey Beltran on September 25, 2010, at
UFC 119. He won the fight via unanimous decision (29–28, 29–28, and 29–28) and also won the
Fight of the Night award. Mitrione defeated
Tim Hague on January 22, 2011, at
UFC Fight Night 23 via TKO in the first round. It was mentioned during the post-fight interview that Mitrione had broken his left hand and later confirmed that he had injured the second metacarpal in his left hand. Mitrione fought
Christian Morecraft on June 26, 2011, at
UFC on Versus 4. Mitrione dominated the first round with his standup scoring two knockdowns. Mitrione ended the fight via KO at 4:28 of round 2 Mitrione suffered his first professional MMA loss to
Cheick Kongo via unanimous decision (30–27, 30–28, and 29–28) on October 29, 2011, at
UFC 137. Mitrione was unable to mount any consistent offense against Kongo on the feet as Kongo used his jab to keep Mitrione at bay, and in the third round Kongo secured a takedown and controlled Mitrione through the end of the fight. Mitrione was expected to face
Rob Broughton on August 4, 2012, at
UFC on FOX 4. However, the bout was scrapped after Broughton pulled out for an undisclosed personal matter. Mitrione/Broughton was briefly linked to
UFC on FX 5 but was eventually scrapped altogether. Mitrione was expected to face
Phil De Fries on December 29, 2012, at
UFC 155. But Mitrione was pulled out of the bout to step in for injured
Shane Carwin against
Roy Nelson at
The Ultimate Fighter: Team Carwin vs. Team Nelson Finale on December 15, 2012. He lost the fight via TKO in the first round. Mitrione vs. De Fries eventually took place on April 6, 2013, at
UFC on Fuel TV 9. Mitrione won the fight via knockout just 19 seconds into the first round. On April 8, 2013, it was announced that Mitrione had his contract suspended by the
UFC after making comments about
male-to-female transgender fighter
Fallon Fox during an interview on The MMA Hour. Mitrione called Fox a "lying, sick, sociopathic, disgusting freak" who he hoped would never fight again, and referred to Fox by male pronouns. Mitrione also criticized the state of
Florida for licensing Fox to fight. The suspension was lifted after two weeks when Mitrione's next fight against
Brendan Schaub was announced. However, in mid-July, Mitrione pulled out of the bout citing an injury and Schaub was pulled from the event as well. The bout eventually took place on September 21, 2013, at
UFC 165. Schaub won the fight via first round submission, giving Mitrione the first submission loss of his professional MMA career. Mitrione faced
Shawn Jordan on March 1, 2014, at
The Ultimate Fighter: China Finale. He won via knockout at 4:59 of the first round. The win also earned Mitrione his first
Performance of the Night bonus award. Mitrione was scheduled to face
Stefan Struve on July 5, 2014, at
UFC 175, but Struve collapsed in the locker room before the fight, leading to a cancellation. Mitrione faced
Derrick Lewis on September 5, 2014, at
UFC Fight Night 50. Mitrione quickly defeated Lewis via first-round knockout. Mitrione faced
Gabriel Gonzaga on December 13, 2014, at
UFC on Fox 13. He won the fight via TKO in the first round. The win also earned Mitrione a
Performance of the Night bonus award. Mitrione faced
Ben Rothwell on June 6, 2015, at
UFC Fight Night 68. He lost the fight by submission in the first round. Mitrione faced
Travis Browne on January 17, 2016, at
UFC Fight Night 81. He lost the fight via TKO in the third round, though the bout was mired in controversy, as Mitrione suffered two eye pokes from Browne throughout the fight. This was the last fight on Mitrione's contract and he opted to test the free agency market.
Bellator MMA On March 14, 2016, Mitrione announced he had signed with
Bellator MMA. Mitrione made his promotional debut against Carl Seumanutafa at
Bellator 157 on June 14, 2016. After being dropped by an overhand right by Seumanutafa, Mitrione recovered on the ground and eventually won the fight via knockout in the first round. Embracing a quick return to the Bellator cage, Mitrione faced
Oli Thompson three weeks later on July 16, 2016, at
Bellator 158. He won the back-and-forth fight via TKO in the second round. Mitrione was scheduled to take on
Fedor Emelianenko at
Bellator 172 on February 18, 2017, in San Jose, California. However hours before the fight Mitrione was forced out of the bout due to kidney stones. The match was rescheduled and took place at
Bellator NYC on June 24, 2017. Early in the first round both fighters knocked each other down, but Mitrione recovered faster and finished Fedor with ground and pound, winning via knockout in round one.
2018 Bellator Heavyweight Grand Prix On February 16, 2018, Mitrione had a rematch with
Roy Nelson at
Bellator 194 in the quarterfinals of the
Bellator Heavyweight Grand Prix tournament. Mitrione went on to win the fight by way of majority decision, avenging his prior loss to Nelson in the process. Mitrione faced
Ryan Bader in the semi-finals at
Bellator 207 on October 12, 2018. He lost the fight via unanimous decision 30–25 (twice) and 30–24, and was eliminated from the grand prix.
Post-GP tenure Mitrione returned to face
Sergei Kharitonov in the main event at
Bellator 215 on February 15, 2019. The bout ended in a No Contest fifteen seconds into the first round after Mitrione landed an accidental groin strike leaving Kharitonov unable to continue. Mitrione faced Kharitonov in an immediate rematch six months later at
Bellator 225 on August 24, 2019. Mitrione's mouthpiece repeatedly fell out of his mouth, and he eventually lost the fight via knockout in the second round. Mitrione stepped in to replace
Josh Barnett, who failed his medical tests, to face
Ronny Markes at
Bellator 241 on March 13, 2020. However, the whole event was eventually cancelled due to the prevailing
COVID-19 pandemic. Mitrione next faced
Timothy Johnson on August 7, 2020, at
Bellator 243. He lost the fight via technical knockout in the first round. Mitrione was expected to face Tyrell Fortune on April 2, 2021, at
Bellator 255. However, during the week of the bout, Mitrione had to pull out and was replaced by Jack May. The bout against Tyrell Fortune was rescheduled again and eventually took place at
Bellator 262 on July 16, 2021. Mitrione lost the bout after submitting to strikes in the first round. Mitrione protested the stoppage due to an accidental clash of heads that occurred before Fortune secured a takedown. After going 0–4 (1) in his most recent five bouts with the promotion, it was announced on July 19, 2021, that Mitrione had been released from Bellator MMA.
Mixed rules venture According to Mitrione, he was scheduled to face
Kubrat Pulev on November 27, 2021, in a boxing vs MMA card promoted by
Triller that featured other UFC veterans. However, the opponents were switched and Mitrione faced boxer
Alexander Flores at the event.
Retirement In November 2021, Mitrione all but stated he was retired from MMA, leaving his career open to mixed rules bouts but probably nothing more. He stated he himself ‘"done with MMA", and that no one had outclassed him in the stand up combat of his MMA bouts. ==Personal life==