But before the main protagonists take centre stage, there are five other main card fights for fans to dig their teeth into on Saturday night.
Robert Whittaker’s clash with Jared Cannonier is effectively a title eliminator for a shot at Israel Adesanya’s middlweight belt and is shaping up to be a stellar co-main event.
Here, Sportsmail previews that fight and the four other match-ups on the main card.
Robert Whittaker is looking for back-to-back wins after the victory over Darren Till
Robert Whittaker (22-5-0) vs Jarod Cannonier (13-4-0)
‘Bobby Knuckles’ is on a mission to retain his middleweight title that was classily taken from him in a huge Antipodean clash with Adesanya in October last year.
After being knocked out his challenger he stated in no uncertain terms that he would string a couple of wins together, climb back up to the top of the mountain and have another go.
Part one of that plan was completed when Whittaker overcame Darren Till by unanimous decision.
That was a high level technical striking contest between two elite fighters and underlined the Australian’s place in the upper echelons of the 185-pound division.
Jared Cannonier is riding high as a middleweight and could earn a title shot next with a win
Now he faces an altogether different challenge with Jared Cannonier talked up as the next No 1 contender.
The 36-year-old won two and lost three at light-heavyweight before moving down with far greater success in the weight class below.
He is undefeated at 3-0 with three stoppage victories over solid opponents in David Branch, Anderson Silva, and Jack Hermansson.
The ‘Killa Gorilla’ would be on a four-fight win streak and have an undeniable claim to the throne if he beat Whittaker.
Adesanya believes he will get the job done and even called out the American after dispatching Paulo Costa earlier this year.
It is No 1 against No 3 in the division in a highly-anticipated co-main event of the evening
The former champion is narrow favourite with bookmakers but things he is better everywhere
UFC 254 FIGHTS:
Main card –
Khabib Nurmagomedov vs Justin Gaethje
Robert Whittaker vs Jared Cannonier
Alexander Volkov vs Walk Harris
Jacob Malkoun vs Phil Hawes
Lauren Murphy vs Liliya Shakirova
Magomed Ankalaev vs Ion Cutelaba
Stefan Struve vs Tai Tuivasa
Alex Oliveira vs Shavkat Rakhmonov
Da-Un Jung vs Sam Alvey
Dana White said at the time: ‘Yeah, that’s the fight if Cannonier wins, and I love that about Israel.
‘He’s ready for who’s next. ‘Who else thinks they can beat me?’ The kid is an absolute stud.’
Despite the interest from both Adesanya and White in Cannonier being his next challenge, Whittaker remains the narrow favourite with bookmakers.
Ahead of the fight he has been full of confidence too, saying: ‘I have had hard fights and I expect a very hard fight in Jared, Jared’s a very hard dude.
‘I’m not sleeping on his skill set, I’m not sleeping on his power. He can beat me.
I could lose. But I don’t think I will.
‘He’s very tough, he’s very powerful, he has knockout power, and he’s resilient, he never goes away.
‘But honestly, I just think I’m better across the board. I think I can take this fight wherever I want it to go.
‘I can lead this dance. I think I can sting him, I can knock him out.
I can do anything I want and I have 15 minutes to do that, which is better than 25, so I’m looking forward to it.’
Alexander Volkov (31-8-0) vs Walt Harris (13-8-0)
Harris’ story will be familiar to MMA fans but perhaps not casual observers of the sport.
His daughter Aniah Blanchard was abducted and killed aged 19 last year, her body found a month after her disappearance. A suspect, identified as Ibraheem Yazeed has been arrested and charged with prosecutors seeking the death penalty.
The tragedy put Harris’ career on hold but he returned in May against Alistair Overeem, a fight he lost in the second round.
He needs a win to stay in and around the top 10 of the heavyweight division and faces No 7 Alexander Volkov.
The Russian is also in need of a win having established himself in the division with five wins out of seven including one over former champion Fabricio Werdum.
Walt Harris (right) lost to Alistair Overeem (left) earlier this year and is looking to bounce back
Defeats by Derrick Lewis and Curtis Blaydes have set him back so a win over Harris is a must to breach the top five once more.
Another loss for either man on Saturday will mean a tricky banana-skin fight next against a hungry up-and-coming challenger.
Volkov believes this is the start of his title run, saying: ‘Every loss makes you step back. We have a lot of examples of fighters who lose their fights and then come back and become a champion.
‘For sure, I’m going for the belt, but for now, to be honest for myself, I need to take some wins to prove to everybody that I’m ready for this.’
Harris added: ‘For 13 weeks, I’ve been preparing for Saturday night. My focus has been laser for this moment and I think that every time I come off a loss, you see a different me. A more focused, more hungry, more driven me. I think that Saturday night, you’re going to see the best me.’
Alexander Volkov wants to break into the top five of the heavyweight division
Jacob Malkoun (4-0-0) vs Phil Hawes (8-2-0)
This is Malkoun’s UFC debut and he boasts a perfect 4-0 record but is relatively inexperienced.
The 25-year-old Australian has trained with Whittaker in the past but it remains to be seen how far he will go at the top level and Saturday should help provide some answers.
Hawes is on a four-fight winning streak, the last of which was in Dana White’s Contender Series and earned him a call-up to the big show.
So both middleweights are newcomers and immediately have a huge stage to impress on and real chance to stamp their authority on the organisation.
While a win will not mean either man moves into a ranked position, the profile boost is inevitably going to help.
Phil Hawes (right) will want to make a strong first impression on his UFC debut
Lauren Murphy (13-4-0) vs Liliya Shakirova (8-1-0)
Shakirova is breaking new ground as the first woman from Uzbekistan to compete in the UFC.
Her record of 8-1 but in truth she is an unknown quantity. Shakirova replaced Cynthia Calvillo to take this match-up with Murphy on short notice and could immediately make a name for herself.
She is a freestyle wrestling champion in her homeland but Murphy is coming off the back of three wins over Romero Borella, Andrea Lee, and Roxanne Modafferi so will be full of confidence.
Shakirova revealed this week that Khabib’s team played a key role in securing her this debut: ‘Khabib’s team traveled to Uzbekistan and negotiated some sort of a bridge for the Uzbekistani fighters to have a way to the UFC or global arenas, she said. ‘They’re heavily involved in those negotiations.’
Lauren Murphy (pictured) will have the experience advantage over Liliya Shakirova
Magomed Ankalaev (13-1-0) vs Ion Cutelaba (15-5-0)
This one has some intrigue around it after the way their first encounter finished.
Back on March 1, the fight was prematurely stopped after Cutelaba pretended he was wobbled by strikes from Ankalaev, fooling the referee into thinking he was actually wobbled and prompting him to step in and stop the contest too soon.
It was immediately rebooked and finally we have the chance to see a rematch with it kicking off the main card this Saturday.
Magomed Ankalaev (right) won the first fight against Ion Cutelaba in controversial fashion
With Jon Jones out of the picture, the light-heavyweight has a new champion in Jan Blachowicz and there is plenty of opportunity for the contenders to rise up.
Ankalaev would have a perfect record if it wasn’t for Paul Craig submitting him in the very last second of the last round of his UFC debut in London back in 2018.
He’s since won four in a row, including the contentious stoppage against Cutelaba.
Cutelaba, a powerful Moldovan, has a patchy record and will be out to exact revenge to potentially force a third fight to settle the score next year.