Julianna graduated in 2007 from Mt. Spokane High School. She then attended Spokane Community College.

Peña made her professional MMA debut in May 2009. She won four consecutive fights but suffered her first defeat in April 2012 to future fellow The Ultimate Fighter 18 cast member Sarah Moras in a 140-pound catchweight bout. The fight took place just two months and one week after Peña was involved in an accident with a drunk driver while walking in downtown Spokane in which she was knocked unconscious and suffered a broken nose. Ten months later she returned to professional competition in a fight in the flyweight division, a move down from the bantamweight division, losing by unanimous decision.

In the semifinals, Peña faced off against Sarah Moras. The two fought previously in a professional bout in 2012, with Peña losing after suffering an injury due to an armbar which forced the doctor to stop the bout between the second and third rounds. Peña won the fight via guillotine choke in the second round to avenge the loss.

In August 2013, it was announced that Peña was one of the fighters selected to be on The Ultimate Fighter: Team Rousey vs. Team Tate.

Peña faced Jessica Rakoczy in the finals on November 30, 2013 at The Ultimate Fighter 18 Finale. She won the bout via TKO in the final seconds of the first round and became TUF 18 women’s bantamweight champion.

Peña was featured in the award-winning mixed martial arts documentary Fight Life, the film is directed by James Z. Feng and was released in 2013.

Peña was expected to face Jessica Andrade at UFC 171 on March 15, 2014. However, Peña pulled out of the bout after suffering an injury to her right knee. She suffered the injury while grappling in training, ultimately damaging, among other aspects, her ACL, MCL, LCL and meniscus. Despite the severity of the injury, doctors have assured Peña that her right knee will return to full strength following surgery and rehabilitation. The injury kept Peña out of action for the rest of 2014.

Peña returned to face Milana Dudieva on April 4, 2015 at UFC Fight Night 63. She won the fight via TKO in the first round. The win also earned Peña her first Performance of the Night bonus award.

Peña next faced Jessica Eye on October 3, 2015 at UFC 192. She won the fight by unanimous decision.

Peña faced former title challenger Cat Zingano at UFC 200 on July 9, 2016. She won the fight by unanimous decision.

Peña faced Valentina Shevchenko at UFC on Fox 23 on January 28, 2017. She lost the fight via armbar submission in the second round.

On October 14, 2017 Peña announced that she was pregnant and would be taking an indefinite hiatus from the sport. On July 13, 2019 at UFC on ESPN+ 13, nearly two and a half years from her last bout, she returned and faced former UFC Women’s Flyweight Championship Nicco Montaño, replacing an injured Sara McMann. She won the fight via unanimous decision.

In January 2018, Peña gave birth to her first child, a daughter.

Peña was expected to face Aspen Ladd on March 28, 2020 at UFC on ESPN 8. However, Peña pulled out of the fight in early March citing an injury.

Peña faced Germaine de Randamie on October 4, 2020 at UFC on ESPN: Holm vs. Aldana. She lost the fight via a guillotine choke in round three.