After finishing runner-up to Lando Norris at the direct-drive Karting World Championship in 2014, Mazepin graduated to junior formulae.

Mazepin signed for Haas in 2021 to partner Mick Schumacher, making his Formula One debut at the Bahrain Grand Prix under a neutral flag representing the Russian Automobile Federation.

[a] After crashing out on lap one of his debut race, Haas failed to score points all season with the VF-21, with Mazepin finishing a career-best 14th in Azerbaijan.

He made his final Formula One start in Saudi Arabia, withdrawing from the Abu Dhabi Grand Prix with COVID-19.

[16][17] In April 2022, a residential compound owned by Nikita and Dmitry in Portisco, Sardinia that was worth more than $114 million was seized by Italian authorities.

[21][22] In March 2024, the EU overturned the sanctions against Mazepin as the association criterion of beyond a simple family relationship did not exist after he was dropped by Haas two years ago.

He then made the switch to compete in the Toyota Racing Series with ETEC Motorsport, where he finished 18th in the drivers' standings.

Mazepin moved to GP3 in 2018 to race for ART Grand Prix alongside Callum Ilott, Jake Hughes and eventual champion Anthoine Hubert.

On the final lap of the Belgian feature race, he pushed Carlin driver Yuki Tsunoda wide, and was given a five-second time penalty, denying himself victory.

[48] His first race in which he beat teammate Schumacher came in Monaco, and Mazepin achieved his best result of the season at the following round in Azerbaijan, largely thanks to four retirements affecting the rest of the grid.

[49] Mazepin missed the season finale at Yas Marina due to a positive COVID-test on race day; he was not replaced for the event.

[51] Mazepin was contracted to compete for Haas in the 2022 Formula One World Championship again under a neutral flag representing the Russian Automobile Federation like the 2021 championship, however on 5 March, Haas terminated both his contract and Uralkali's title sponsorship as part of the larger global response to the 2022 Russian invasion of Ukraine.

[52] Mazepin expressed disappointment at the decision, remarking on social media that his "ongoing willingness to accept the conditions proposed in order to continue were completely ignored".

[57][59][60][61] A self-professed rally raid fan, Mazepin participated in a test with Dakar Rally-winning truck team Kamaz Master in July 2021.

In his July 2022 interview with Match TV, Mazepin explained he intended to compete in off-road as long as he enjoyed it, and joked he would continue to do so if he could "physically walk and get into the car" as "there is no age limit in this sport.

"[58] To gain experience, he began training with former Dakar quad category winner Sergey Karyakin and his Snag Racing team.

Karyakin described Mazepin as knowing "how to read the lines perfectly, he sees the dunes" and that "bearing in mind that it was the first time he tested the sand, the results were quite good.

[72] He and Jani finished fourth in the LMP2 driver's championship with a sixth in the second Dubai race, followed by seventh and second in the two Abu Dhabi rounds.