Murphy said about starting martial arts: "I took my son to a Jiu Jitsu class in late 2009, and I took the class with him to encourage him. I fell in love with it and started going all the time. I began training MMA about 3 months later, and took my first pro fight 3 months after that. I did not have any amateur fights."
Murphy began her pro MMA career in Alaska on June 9, 2010, fighting in the featherweight division. She won four straight fights and captured two featherweight titles; one for Alaska Fighting Championship and one for the now-defunct promotion Alaska Cage Fighting. After moving to Florida, Murphy stepped in on short notice to face Jennifer Scott in a bantamweight bout at Legacy Fighting Championship 18 on March 1, 2013. She defeated Scott by TKO in the first round.
On July 3, 2014, it was announced that Murphy had signed with the UFC. She made her debut against Sara McMann at UFC Fight Night 47 on August 16, 2014. McMann won the fight by split decision. Murphy faced Liz Carmouche on April 4, 2015 at UFC Fight Night 63. She lost the fight by unanimous decision. Murphy faced Kelly Faszholz on February 21, 2016 at. She won the fight via TKO due to punches and elbows in the final seconds of the third round. The win also earned Murphy her first Fight of the Night bonus award. Murphy face Katlyn Chookagian on July 13, 2016 at. She lost the fight via unanimous decision.
In August 2017, it was announced that Murphy would be one of the fighters featured on The Ultimate Fighter 26, where the process to crown the UFC's inaugural 125-pound women's champion will take place. Murphy, representing team Alvarez, was seeded third and therefore was automatically set to fight fourteenth seed Nicco Montaño. She lost the fight via Unanimous Decision in two rounds, eliminating her from the competition. Later, feeling discontent with her training on Team Alvarez, she switched teams to Gaethje.
UFC return
Murphy was scheduled to face Priscila Cachoeira on December 1, 2017 at. However, due to a visa issue, the fight was cancelled and Murphy was asked to be ready to fight as an alternate. With Roxanne Modafferi elevated to the main event to fight Nicco Montaño after Sijara Eubanks was medically disqualified from the title fight, Murphy stepped in to face Barb Honchak. Murphy won the back-and-forth fight by split decision. Murphy faced Sijara Eubanks at on June 1, 2018. She lost the fight via unanimous decision. Murphy was scheduled to face Ashlee Evans-Smith on February 17, 2019 at UFC on ESPN 1. However on December 19, 2018 Murphy announced and withdraw from the event as she would need more time off to recover from foot surgery. Murphy faced Mara Romero Borella on August 3, 2019 at UFC on ESPN 5. She won the fight via TKO in the third round. Murphy faced Andrea Lee on February 8, 2020 at UFC 247. She won the fight via controversial split decision. 12 out of 12 MMA media outlets scored the contest for Lee with none scoring it for Murphy, despite Murphy achieving a higher degree of accuracy and securing the only two takedowns in the fight. Murphy faced Roxanne Modafferi on June 20, 2020 at. She won the fight by unanimous decision.
