At 10 years old, Ngannou started working in a sand quarry in Batié because of a lack of funds.

[23] However, Ngannou refused and instead decided to use his father's negative reputation as a street fighter as motivation to do something positive and pursue boxing.

[23] At age 22, Ngannou began training in boxing, despite the initial reluctance of his family.

[24] He did various odd jobs to make ends meet, until age 26 when he decided to head to Paris, France, to pursue professional boxing.

Carmont convinced the gym to let him train at no cost, and introduced Ngannou to the sport of MMA.

[27] When his boxing gym closed for the summer, Lo Chorba's director Khater Yenbou introduced Ngannou to Fernand Lopez and the MMA factory.

Reflecting on his journey across continents and his decision to become an MMA fighter, Ngannou said:[20][25]When I started, I had nothing.

The last time I was in Cameroon, I brought a lot of materials for boxing and MMA to open a gym.

[33] He won the fight via TKO, due to doctor stoppage at the end of the second round.

[34] In his next bout, Ngannou faced another newcomer in Bojan Mihajlović on 23 July 2016, at UFC on Fox 20.

[37] He won the fight by submission in the first round, and earned his first UFC Performance of the Night bonus.

[42] However, on 18 August, Dos Santos was pulled from the match after being notified of a potential USADA violation.

[43] In turn, Ngannou was removed from the card after promotion officials deemed that a suitable opponent could not be arranged.

[46][17][47] In the highest profile fight of his career, Ngannou faced veteran Alistair Overeem on 2 December 2017, at UFC 218.

The fight was heavily criticized by the media and the fans for the lack of offence from both competitors[57][58][59][60] and was labeled as a "snoozefest".

[72] However, on 9 April, Dana White, the president of the UFC announced that the event was postponed[73] and the bout eventually took place on 9 May 2020.

[86] On 16 May 2023, it was announced that Ngannou had signed a multi-fight deal with the Professional Fighters League (PFL).

[90][91] Ngannou's PFL contract has been called a historic moment for the sport,[92] with Daniel Cormier saying it sets "a new standard for what is out there in the [MMA] free-agent market.

"[93] John S. Nash of Bloody Elbow and Alex Pattle of The Independent each referred to a different aspect of the deal as "unprecedented".

[97] Ngannou took on the undefeated WBC and Lineal heavyweight champion Tyson Fury in a professional boxing match billed as "Battle of the Baddest" on 28 October 2023, in Riyadh, Saudi Arabia.

"[104] Ngannou faced Anthony Joshua on 8 March 2024 in Riyadh, Saudi Arabia,[105] and lost by second-round knockout.

[114] The Francis Ngannou Foundation, initially run solely on Ngannou's personal funds and later combining that with donations, runs the first MMA gym in Cameroon, aiming to offer facilities for young people to have a place to train.

It also donates educational materials to Cameroonian children and schools, including setting up computer labs in underserved villages.