Islam was born in Makhachkala, Dagestan of Lak ethnicity. He trained and competed in combat sambo. Islam grew up with Khabib Nurmagomedov and still trains with him to this day. In 2016 World Combat Sambo Championship he won a gold medal, in the final match he won 7–0 over Valentin Benishev of Bulgaria.
Makhachev made his M-1 Global debut against Tengiz Khuchua on February 12, 2011 and won the fight via KO in the first round. In his second fight for the promotion, Makhachev faced Mansour Barnaoui, on April 9, 2013 at M-1 Challenge 38. He won via unanimous decision. Makhachev faced undefeated Brazilian Jiu-Jitsu black belt Rander Junio on August 21, 2013 at M-1 Challenge 41. He won via unanimous decision. Makhachev faced M-1 Global Yuri Ivlev on June 7, 2014 at M-1 Challenge 49. Islam dominated the fight, he softened up Ivlev with punches before finishing the fight by submission via armbar. On September 7, 2014, in his final bout for M-1 Global before signing with the UFC, Makhachev defeated Ivica Truscek via submission in the third round.
Ultimate Fighting Championship
On October 2, 2014, Makhachev signed a four-fight contract with the UFC. Makhachev submitted Leo Kuntz in the second round on May 23, 2015, at UFC 187. Makhachev lost by first-round technical knockout to Adriano Martins at UFC 192 on October 3, 2015. Makhachev was expected to face Drew Dober on April 16, 2016, at UFC on Fox 19. After the weigh ins, the UFC announced that Makhachev had failed an out-of-competition drug screening, testing positive for the banned anti-ischemic meldonium. The match was cancelled. USADA lifted the suspension of Makhachev after a hearing on July 2, 2016. Makhachev returned to face Chris Wade on September 17, 2016 at UFC Fight Night 94. He won the fight via unanimous decision. Makhachev faced Nik Lentz on February 11, 2017, at UFC 208. He won the fight by unanimous decision. Makhachev was expected to face Michel Prazeres on September 2, 2017 at UFC Fight Night 115. However, Makhachev pulled out of the fight in the beginning of August citing a religious reason, and he was replaced by Mads Burnell. Makhachev faced Gleison Tibau on January 20, 2018 at UFC 220. He won the fight by knockout in 57 seconds in the first round. Makhachev faced Kajan Johnson on July 28, 2018 at UFC on Fox 30.. Makhachev took Johnson down in the first round, where he worked to mount and secured the armbar, forcing Johnson to tap; giving Makhachev a submission victory. Makhachev was expected to face Francisco Trinaldo on January 26, 2019 at UFC 233. However, it was reported on November 11, 2018 Makhachev was pulled out from the event due to undisclosed reason and he was replaced by Alexander Hernandez. Makhachev faced Arman Tsarukyan on April 20, 2019 at UFC on ESPN+ 7. He won the fight via unanimous decision. This win earned him the Fight of the Night award. Makhachev faced Davi Ramos on September 7, 2019 at UFC 242. He won the fight via unanimous decision. Makhachev was expected to face Alexander Hernandez on April 18, 2020 at UFC 249.; However, Russia restricted air travel due to the COVID-19 pandemic, Makhachev was forced to removed from the event and he was replaced by Omar Morales.
