Duffee was born in Evansville, Indiana but grew up in Raleigh, Illinois as the fourth son of a salt miner father and nurse mother. Duffee played many sports growing up, including baseball, football, track, bull riding, soccer, and basketball. Duffee also began training in boxing but was not very devoted to it as he was playing other sports. A standout football player, he was signed on to play college football but his career was derailed from an injury. Duffee then moved to Atlanta, Georgia when he was 18 years old and continued boxing, before watching a UFC event and shifting his training to mixed martial arts. He was working on a degree from the University of Georgia before leaving to train MMA full-time. As of February 2016, he is pursuing a degree in business from the University of Georgia.
Duffee won his first three fights against Mike Walbright, Mark Haniger and Josh Bennett. Duffee then agreed to fight UFC and PRIDE FC veteran, Assuério Silva in the main event of Jungle Fights 11. Duffee dominated the fight and won by knockout in the second round.
Duffee was set to make his UFC debut against Mostapha al-Turk at UFC 99 until the UFC pulled Duffee from the fight. Duffee was replaced by Mirko Filipović. He was next announced by the UFC to face fellow UFC newcomer Mike Russow. However, Duffee was then pulled from that match and instead was matched up against Tim Hague at UFC 102. Duffee set the record for the fastest KO in UFC heavyweight history (0:07) after flooring Hague with a stiff jab and rendering him unconscious with follow-up ground and pound. After the finish, he celebrated to the camera by saying "That was an appetizer, I want to eat now Dana, let me eat!"
Duffee was expected to face Paul Buentello at UFC 107 but pulled out due to a back injury.
Duffee fought Mike Russow at UFC 114 in which he lost via KO in the third round. Prior to the fight Duffee went on record to say that he was being overhyped by the MMA world, while his opponent was very much underrated. After dominating the first two rounds by utilizing his boxing, Duffee looked to be on his way to a unanimous decision win, when, from out of nowhere, Russow caught Duffee with two straight right hands followed by a hammerfist that prompted the referee to stop the fight as Duffee laid unconscious on the canvas. Joe Rogan stated that the nature of the knockout was "like something out of a movie" and was "one of the greatest comebacks in UFC history". Russow broke his left ulna while deflecting Duffee's punches at the end of round 1. After the fight it was revealed that Duffee fought with a torn MCL as well as Shingles of the eye.
Duffee was expected to face Jon Madsen on October 23, 2010 at UFC 121, but Duffee was once again forced off the card due to injury and replaced by Gilbert Yvel.
On September 7, 2010, Duffee was surprisingly released from the UFC for unknown reasons. It is rumored that Duffee requested financial aid in order to pay for a knee surgery which he couldn't afford, but when UFC said that he must pay for it himself there was a dispute between the two parties. Duffee spoke publicly about MMA fighters being underpaid and how he needed to take a second job just to pay for his training. Dana White later said in an interview with Ariel Helwani that Duffee had an attitude problem and that it seemed to him that "he doesn't want to be in the UFC, he doesn't like being in the UFC." He also said that he could work his way back into the organization via fighting in smaller leagues. Following his release Duffee said that he couldn't understand his release and has never been told why, although he harbors no bitterness towards the UFC president or the company.
After his release from the UFC, Duffee was scheduled to compete in Titan FC in the beginning of 2011. However, when DREAM, a promotion based out of Japan, was unable to secure an opponent for former Strikeforce Heavyweight Champion Alistair Overeem in DREAM's first Heavyweight Championship bout at Dynamite!!, Duffee had his manager throw his name in the mix of potentials for the bout. Less than two weeks before the event, he was officially named to take on Overeem in the title fight, leaving him very little time to prepare but an opportunity to fight a big name in the Sport. As the bout started Duffee charged in very aggressively flurrying punches to no avail, and the veteran Overeem stayed calm and landed a knee that rocked Duffee then followed by punches that put Duffee out cold at 19 seconds of the first round. Duffee said after the fight that he respected Overeem's ability but felt that if he had sufficient time to train and prepare that it would have been a completely different outcome. Overeem brought Duffee in for his training camp in preparation for his UFC debut vs. Brock Lesnar in late 2011 in order for Duffee to help him with his takedown defense.
Duffee was scheduled to face Nick Gaston on July 16, 2011 at DREAM 17, but an injury forced him to withdraw from the event.
In February 2012 Duffee signed an exclusive four-fight deal with Super Fight League, India's first professional Mixed Martial Arts fighting league launched and owned by Raj Kundra & Sanjay Dutt. He faced fellow UFC veteran Neil Grove on the SFL's second show held on April 7, 2012. He won via TKO after just 34 seconds in the first round, following up a right-hook that dropped Grove with heavy ground-and-pound. After the fight he thanked his training partners at the American Kickboxing Academy and credited them with helping him through a rough training camp, and stated that he is looking to fight again as soon as possible, adding that he "missed this". Shortly after his win, with SFL taking a 4-month break until their next event it was revealed that Duffee would be allowed to fight outside of the organization that summer if he could find fights. Duffee was appealing to promoters on Twitter for fights in both MMA and Professional Boxing but none came to fruition by the time of SFL's next event.
Duffee was originally announced to fight at SFL 4 on September 29 against former UFC title contender Jeff Monson but after the event was pushed back twice the SFL decided to change the structure of their shows, with weekly events replacing monthly events. Duffee and SFL agreed his departure in September and he returned to free agency. Though frustrated by his fight with Monson falling out, the departure was amicable.
Duffee made his UFC return against Phil De Fries on December 29, 2012 at UFC 155, as a replacement for Matt Mitrione. Despite fighting with a respiratory infection he won the fight via first-round TKO, weathering an early ground exchange before finishing De Fries on the feet. The performance earned Duffee Knockout of the Night honors.
After the De Fries fight it emerged that Duffee had fought with an undisclosed injury sustained during his training camp and would be ruled out for much of 2013. He returned to training after successfully rehabbing the injury in September. However, 3 weeks into his return to the gym, after waking up with severe pains and numbness in his arm Duffee was diagnosed with an unknown affliction which was later revealed to be Parsonage–Turner syndrome. Despite initially being told by doctors that he would not be able to return for at least two years, Duffee returned to training after six months and in September 2014 announced that he was ready to fight.
Duffee returned from his extended hiatus to face Anthony Hamilton on December 6, 2014, at UFC 181. The fight marked his first fight since returning to American Top Team since departing amicably in 2009. He won the fight via knockout in the first round.
Duffee faced Frank Mir in the main event at UFC Fight Night 71 on July 15, 2015. He lost the fight by 1st-round knockout after being dropped by a left hook.
Duffee was expected to face Mark Godbeer on March 4, 2017, at UFC 209. However, Duffee pulled out of the fight in mid-February for undisclosed reasons. It was later revealed that Duffee had sustained a shoulder injury which required surgery. Duffee later stated that he expects to return to fighting in December 2017.
In 2011 Duffee made his film debut in the Michael Jai White-produced Never Back Down 2: The Beatdown, portraying Tim Newhouse, a talented MMA fighter who lives in relative poverty and has to deal with losing his father. He also had a cameo in Batman v Superman: Dawn of Justice in a fight scene.Ultimate Fighting Championship
Fastest knockout (0:07 seconds) in UFC Heavyweight division history.
Knockout of the Night (One time).