Jones made his UFC debut against Andre Gusmão at UFC 87 on August 9, 2008. Jones accepted the deal on two weeks' notice as a late replacement for Tomasz Drwal. He put on an impressive performance, using takedowns and displaying unorthodox striking, such as spinning elbows and a spinning back kick. Jones took a unanimous decision victory.

On December 5, 2009, in his bout with Matt Hamill, Jones was disqualified for using illegal elbows. However, despite instant replay being used to make the decision, Dana White still claimed that the loss should not have counted and should have been a no contest.

Jones defeated former IFL Light Heavyweight Champion Vladimir Matyushenko by TKO with elbows in 1:52 of the first round on August 1, 2010, at UFC Live: Jones vs. Matyushenko. UFC President Dana White promised Jones a "huge step-up in the competition", if he managed to defeat Matyushenko.

On March 19, 2011, Jones was en route to Great Falls Historic Park in Paterson, New Jersey, where he planned to meditate several hours ahead of his fight against Maurício "Shogun" Rua at UFC 128. He was accompanied by his coaches Mike Winkeljohn and Greg Jackson. As their driver prepared to drop them off, Jones observed an elderly couple screaming for help. The woman informed Winkeljohn that a man had smashed her car window and had run off with her GPS. Jones, along with his two coaches, chased after the robber, caught and tripped him, and held him down until the police arrived.

UFC 151, scheduled to premiere on September 1, 2012, was cancelled due to Jones declining to fight Chael Sonnen, a last-minute replacement for Dan Henderson. In the 19-year history of the UFC, it was the first card to ever be cancelled. UFC President Dana White went on record saying, "this is one of the most selfish, disgusting decisions that doesn't just affect you. This is affecting 16 other lives, their families, kids are going back to school. The list goes on and on of all the things, the money that was spent for fighters to train and the list goes on and on. Like I said, I don't think this is going to make Jon Jones popular with the fans, sponsors, cable distributors, television network executives or other fighters."

Jones faced Alexander Gustafsson on September 21, 2013, at UFC 165. Jones was badly cut above the eye during the first round, but he powered through it, and eventually won the back-and-forth fight via a controversial unanimous decision (48-47, 48-47, 49-46). After the match, Jones said Gustafsson gave him the toughest fight of his career, and both were sent to the hospital for their injuries. Both men suffered lacerations and facial swelling, though Jones' appeared to be worse for the wear. Both combatants were released from the hospital with no broken bones or serious injuries. The bout also earned both fighters the Fight of the Night bonus award. The match received numerous positive characterizations: "an epic battle", "instant-classic", "Fight of the Year", "Greatest light heavyweight title fight of all-time", "one of the greatest fights in UFC history".

During a promotional event for UFC 178, Jones and Daniel Cormier briefly scuffled during an on-stage staredown, initiated by Jones pressing his forehead against Cormier's forehead, prompting Cormier to shove Jones by the throat. Both fighters were restrained by coaches and event organizers. UFC chief legal officer Kirk Hendrick said "there are going to be ramifications". In addition, the Nevada State Athletic Commission requested a video copy of the altercation. On September 23, 2014, Jones was fined $50,000 fine and was ordered to undergo 40 hours of community Service by the Nevada Athletic Commission. During the disciplinary hearing, Jones claimed losing a six-figure endorsement deal with Nike, but later admitted to fabricating the statement.

On September 29, 2015, Jones pleaded guilty to leaving the scene of an accident and was subsequently sentenced to up to 18 months of supervised probation. He was authorized to travel for work-related purposes. Jones met all of the conditions, which included 72 separate appearances for charity or youth outreach, avoiding a felony charge on his Criminal record.

On November 7, 2016, it was announced that Jones was issued a 1-year suspension by USADA following his arbitration hearing, though the arbitration panel concluded that Jones did not take the banned substances intentionally, and was not a drug cheat.

On August 22, 2017, it was announced that Jones was flagged for a potential doping violation by USADA, stemming from his test sample that was collected after weigh-ins July 28. He allegedly tested positive for Turinabol, an anabolic steroid. Jones was placed on a provisional suspension as a result of the positive drug test, and was afforded a full adjudication process. On September 13, 2017, the CSAC announced that it had overturned the result of the fight to a no-contest after Jones' B sample tested positive for Turinabol. Jones stated that he did not knowingly take any prohibited substances. His team believed that Jones consumed tainted substances. If found guilty, Jones could face up to a 4-year suspension.

Jones has been criticized for repeatedly poking his opponents in the eyes. In response to the criticism, Jones released a video over Instagram, in which he mocked fans by crying like a baby, which has since been deleted. Dana White went on record stating, "we've got to stop that stuff. The openings of the hands and putting the hands on the face are something bad, but it happens with guys who have reach. They do that a lot." White later clarified his point, saying, "It's not just taller fighters. Jones has that range and he can do it, but lots of guys do it because that’s how you block punches. So you keep your hands open and you slap punches down. Then guys are rushing in and you’re doing whatever, and guys get poked in the eyes." He also noted that in the fight against Glover Teixeira, after Jones was warned about the behavior, he was more careful to avoid any eye pokes throughout the rest of the match. He also stated that Jones would likely not receive any credit for that from detractors. Jones later responded to the controversy in an interview, saying, "I realize that I do it. I realize the criticism that I got from it. It’s not on purpose. If you watch my fights, a lot of the times when guys get poked in the eyes, it’s me extending my arm in a reactionary way. I do put a hand on people’s foreheads to maintain distance. That’s what you saw in the Teixeira fight, but to say I am purposely poking people in the eye, it’s just inaccurate. You can call it what you want."