Lewis earned the shot at the title after beating Alexander Volkov barely a month ago, but his quick return to the octagon failed to pay off after he tapped out in the second round of the clash in New York.
American Cormier controlled the bout from the start, grabbing a takedown after barely a minute in the first round.
Cormier got stung by a right hand from Lewis in the second but the champion soon had his opponent back on the canvas, a rear-naked choke finishing the job at 2.14.
With the the victory, Cormier has become the first man to defend both the light-heavyweight and heavyweight belts.
Quoted on the UFC website, Cormier said after the fight: “There are no surprises with me. I come in here and try to do my thing.
“If you come in here with a puncher’s chance, it’s not enough. You have to be one of the best in the world to be able to compete. Derrick is good, but he’s not at that level yet.”
Before the main event, Karl Roberson earned a convincing unanimous decision over Welshman Jack Marshman in their middleweight bout.
Marshman was looking to bounce back after his loss against Antonio Carlos Jr last month, but was denied after three rounds at Madison Square Garden.
Former kickboxer Roberson, on the back of suffering his first pro defeat against Cezar Ferreira at UFC 224, set the tone in the first round, attempting an early head kick which was blocked by Marshman.
Marshman struggled to land his punches and did his best to find his target with leg kicks, but was sent to the fence by a series of left hands from Roberson.
In the second, Marshman came out strong, unleashing a barrage of blows, but a takedown from Roberson looked to have secured him the round.
The 28-year-old continued to dominate with his left hand in the third, winning the decision victory 30-26, 30-26, 30-27.
Arabian Gulf League side Al Wahda welcomed UFC lightweight champion Khabib Nurmagomedov to the Al Nahyan Stadium on Wednesday.
The Abu Dhabi side posted pictures on their social media accounts of the Russian fighter posing with fans and officials with his own Al Wahda shirt.
The 30-year-old is on vacation in the UAE just three weeks after his victory over Conor McGregor at UFC 229.
Both fighters are currently suspended pending an investigation by the Nevada State Athletic Commission following a melee which broke out after their bout on October 6.
The Nevada Commission reportedly voted to uphold temporary suspensions for both fighters until a hearing in December.
The commission voted to release half – $1million – of Nurmagomedov’s purse after initially holding all of his earnings.
The other half of the Russian’s prize money will be withheld until after the disciplinary hearing.
Conor McGregor admitted he was “beaten fair and square” by Khabib Nurmagomedov at UFC 229 but stressed he would not repeat his mistakes in any rematch.
McGregor tapped out to the undefeated Russian in the fourth round of their lightweight title bout in Las Vegas on October 6 as he made his return to mixed martial arts after a near two-year hiatus.
The fight was followed by a mass brawl that led to both men receiving temporary suspensions from the Nevada State Athletic Commission.
McGregor, who has spoken of his desire for a rematch in social media posts since the event, broke his silence about the fight itself with a lengthy Instagram post in the early hours of Tuesday morning.
The Irishman did not mention the post-fight melee, but instead broke down the bout round-by-round.
In the message, McGregor wrote: “Although winning the early exchanges in 4, he dips under again and I end up in a bad position with over 3 on the clock. I work to regain position and end up upright, with my back to the fence. A stable position.
“Here however, I made a critical error of abandoning my over hook at this crucial time, exposing the back, and I end up beaten fair and square.
“What can I say? It was a great fight and it was my pleasure.
“I will be back with my confidence high. Fully prepared.
“If it is not the rematch right away, no problem. I will face the next in line.”
The 30-year-old admitted he had underestimated parts of Nurmagomedov’s fighting style and said it would not happen again.
McGregor said: “Round 2 he is running away around the cage before being blessed with a right hand that changed the course of the round, and the fight. It was a nice shot.
“I gave his upright fighting no respect in preparation. No specific stand up spars whatsoever.
Attacking grapplers/wrestlers only. That won’t happen again.”
McGregor went on to say the second round was “the worst round of my fighting career” but felt he had come back strongly by winning the third.