Legacy Fighting Alliance Barber made her professional debut against Itzel Esquivel at
LFA 14 on June 23, 2017. She won the fight by a first-round armbar submission. Barber was booked to face
Mallory Martin at
LFA 22 on September 8, 2017. She won the fight by unanimous decision. Barber faced Kaila Thompson at
LFA 33 on February 18, 2018. She won the fight by a first-round submission. Barber faced Audrey Perkins at
LFA 39 on May 4, 2018, in her final fight with the promotion. She won the fight by a second-round technical knockout, the first knockout victory of her professional career. Mayce Barber faced Jamie Colleen at
Dana White's Contender Series 13 on July 17, 2018. She received a
UFC contract after earning a stoppage in the third round.
Ultimate Fighting Championship Barber made her UFC debut on November 10, 2018 on
UFC Fight Night 139 against
Hannah Cifers. She won the fight via TKO in round two. Barber faced
JJ Aldrich at
UFC Fight Night 148 on March 23, 2019. Barber won the fight via technical knockout in round two. Barber faced
Gillian Robertson on October 18, 2019 at
UFC on ESPN 6. She won the fight via technical knockout in round one. Barber faced
Roxanne Modafferi on January 18, 2020 at
UFC 246. In an upset, she lost the one-sided fight by unanimous decision. After a year of hiatus recovering from a knee injury, Barber faced
Alexa Grasso on February 13, 2021 at
UFC 258. She lost the fight via unanimous decision. Barber faced
Miranda Maverick on July 24, 2021 at
UFC on ESPN 27. She won the fight via controversial split decision. 22 out of 22 media outlets scored the bout as a win for Maverick. Barber was expected to face
Montana De La Rosa on December 11, 2021 at
UFC 269. However, De La Rosa pulled out of the fight in early October citing injury and she was replaced by
Erin Blanchfield. In turn, Barber withdrew in early November due to undisclosed reasons. Barber faced
Montana De La Rosa on April 23, 2022 at
UFC Fight Night 205. She won the fight via unanimous decision. Barber, replacing injured
Casey O'Neill, faced
Jessica Eye on July 2, 2022, at
UFC 276. She won the bout via unanimous decision. The bout also marked the last of her prevailing contract, and she re-signed with the UFC later in the year. Barber faced
Andrea Lee on March 25, 2023, at
UFC on ESPN 43. She won the bout via split decision. Barber faced
Amanda Ribas on June 24, 2023 at
UFC on ABC 5. She won the bout in the second round, defeating Ribas via elbows and punches on the ground. The win earned Barber her first
Performance of the Night award. She won the bout by unanimous decision. Barber was scheduled to face
Rose Namajunas on July 13, 2024, at
UFC on ESPN 59. However, Barber withdrew from the bout, due to what was later revealed to be ongoing health problems, and was replaced by
Tracy Cortez. Barber was scheduled to face
Erin Blanchfield in the main event on May 31, 2025 at
UFC on ESPN 68. At the weigh-ins, Barber weighed in at 126.5 pounds, half a pound over the women's flyweight non-title fight limit. The bout was set to be at catchweight and Barber was to be fined 20 percent of her purse which was to go to Blanchfield. However, minutes before the walkouts were to take place, Barber had to withdraw due to a medical issue involving a seizure and the bout was cancelled. Barber faced
Karine Silva on December 6, 2025 at
UFC 323. She won the fight by unanimous decision. Barber faced
Alexa Grasso in a rematch on March 28, 2026, at
UFC Fight Night 271. She lost the fight by knockout in the first round. ==Personal life==