Women's bantamweight

On April 18, 2013, it was announced that de Randamie would make her Ultimate Fighting Championship debut on July 27, 2013.^[10]

De Randamie debuted against Julie Kedzie at UFC on Fox 8. Relying mostly on clinch work, Germaine won the fight via split decision (30–27, 28–29, and 29–28).^[11]

De Randamie next faced Amanda Nunes at UFC Fight Night 31 on November 6, 2013.^[12] She lost the fight via TKO in the first round.^[13][14]

De Randamie next faced Larissa Pacheco at UFC 185 on March 14, 2015. She won the fight via TKO in the second round. ^[15]

Women's featherweight

De Randamie faced former bantamweight champion, Holly Holm, at UFC 208 for the inaugural UFC Women's Featherweight Championship on February 11, 2017. She won the fight via unanimous decision.^[16] At the end of the second and third rounds, de Randamie continued to throw punches after the horn had sounded. The first of those punches was a right hand that visibly wobbled Holm, who had already stopped fighting. The referee, however, did not take a point on either occasion, which affected the result of the fight and drew criticism from UFC president Dana White.^[17][18] Of the media outlets that reported on the fight, 14 of 23 media outlets scored the bout in favour of Holm.^[19] After the fight, de Randamie stated that the blows after the horn were unintentional.^[20] In contrast, Holm stated that she believed de Randamie's punches after the horn was intentional.^[21]

Stripping of Women’s Featherweight Championship

In late May, de Randamie released a statement over social media that she plans to move back to the bantamweight division and rejected the fight with Cris Cyborg due to her repeated transgressions with PEDs.^[22][23] Her decision on not wanting to fight Cyborg drew criticism from many in the media by claiming she was avoiding Cyborg and ignoring her responsibility as a champion to fight any and all challengers.^[24][25][26] In turn, the promotion stripped her of the title on June 19, 2017.^[27][28] Instead, the newly signed Megan Anderson replaced her and was slated to face Cyborg for the UFC Women's Featherweight Championship at UFC 214, before Anderson herself was then replaced by Invicta Bantamweight Champion Tonya Evinger.^[29]

Returning to bantamweight division

De Randamie was expected to face Marion Reneau on September 2, 2017, at UFC Fight Night 115. However, de Randamie pulled out citing injury and was replaced by Talita Bernardo.^[30]

A bout against Ketlen Vieira was announced for UFC Fight Night 125 on February 3, 2018. However, the bout was soon canceled due to a hand injury sustained by de Randamie.^[31]

De Randamie faced former title challenger Raquel Pennington at UFC Fight Night 139 on November 10, 2018.^[32] She won the fight via unanimous decision.^[33]

On March 8, 2019, de Randamie signed a new 6-fight contract with the UFC.^[34]

De Randamie faced Aspen Ladd on July 13, 2019, at UFC Fight Night 155.^[35] She won the fight via technical knockout in round one.^[36]

De Randamie faced Amanda Nunes in a rematch, on December 14, 2019, at UFC 245 for UFC women's bantamweight title fight.^[37] She lost the fight via unanimous decision.^[38]

De Randamie faced Julianna Peña on October 4, 2020 at UFC on ESPN: Holm vs. Aldana.^[39] De Randamie defeated Peña via guillotine choke, the first submission win in her career. ^[40] This win earned her the Performance of the Night bonus.^[41]

De Randamie was next expected to face Irene Aldana at UFC 268 on November 6, 2021, in New York. ^[42] However, de Randamie withdrew in early September due to injury.^[43]

After a 3-year and six-month hiatus, de Randamie returned to the octagon and faced Norma Dumont on April 6, 2024, at UFC Fight Night 240.^[44] She lost the bout by unanimous decision.^[45]