It marks a return to drivetime for Mayo, who presented the slot on BBC Radio 2 from 2010 to 2018. He quit the station after an unsuccessful pairing with Jo Whiley.
The DJ will make the switch between Bauer Media stations from March 15.
“Returning to drivetime is so very exciting for me. It’s a show I loved so much and now on Greatest Hits Radio we intend to make it even better,” said Mayo. “And with Matt Williams back on sport, we can’t wait to get started. The message of the show is the same-enjoy yourself, it’s later than you think!”
Mayo had been presenting a daytime show on the classical-leaning Scala for the last two years. He will launch a weekend show on the station, which will be announced in due course.
Mark Forrest will take on Scala’s 11am-1pm show, with a full new Spring schedule to be announced later this month.
“We’re so excited to have one of the UK’s most loved radio presenters hosting an all new drivetime Show on Greatest Hits Radio,” said Gary Stein, group programme director for the Hits Radio Brand Network.
“With Simon playing the amazing music that the nation grew up with from the ’70s, ’80s and ’90s along with his warmth and personality, I know audiences will love his new show”.