After going undrafted during the 2017 NFL Draft, Mullens signed as an undrafted free agent with the San Francisco 49ers on May 4, 2017.[7] He was waived by the team on September 2, 2017 and was signed to the practice squad the next day.[8][9] He signed a reserve/future contract with the 49ers on January 2, 2018 after spending his entire rookie season on the practice squad.[10]
On September 1, 2018, Mullens was waived by the 49ers and was signed to the practice squad the next day.[11][12] Mullens was promoted to the active roster on September 26 after starter Jimmy Garoppolo suffered a season-ending torn ACL.[13] Following an injury to C.J. Beathard, Mullens was named the starter for the week nine game against the Oakland Raiders on Thursday Night Football.