The Carolina Panthers selected Mayo in the fifth round (169th overall) of the 2015 NFL draft.[4] He signed his four-year rookie contract, worth $2.44 million contract, on May 7, 2015.[5][6] Mayo was part of the Panthers team that played in the Super Bowl 50 loss to the Denver Broncos.[7]
San Francisco 49ers
On March 14, 2019, Mayo signed a two-year contract with the San Francisco 49ers.[8] He was released on August 31, 2019.[9]
New York Giants
On September 2, 2019, Mayo was signed by the New York Giants.[10] In Week 5 against the New England Patriots, Mayo recorded a team high 13 tackles and a sack.[11] On March 16, 2020, Mayo signed a three-year contract extension with the team.[12] On September 6, 2020, he was placed on injured reserve with a torn meniscus before being activated on October 16, 2020.[13][14] Mayo was released on March 4, 2021.[15]
Washington Football Team / Commanders
Mayo signed with the Washington Football Team on March 18, 2021.[16] He was released on August 31, 2021,[17] but re-signed with the team the following day.[18] On December 13, 2021, he was placed on the COVID-19 reserve list.[19] After missing the Week 15 game against the Philadelphia Eagles, he was placed back on the active roster on December 23.[20]
On January 28, 2022, Mayo signed a one-year contract extension with Washington.[21] He re-signed on another one-year contract on February 24, 2023.[22]