The Radio 2 Drivetime show with Simon Mayo and Jo Whiley is to end after just a few months on air.
Mayo is leaving BBC Radio 2 altogether but will continue to present his 5 Live film show with Mark Kermode.
Whiley will remain on the station but move to the 7-9pm slot, which means Drive will get a brand new presenter.
Mayo has fronted Drivetime for eight years, but the station added Whiley as a co-host in May - a move which led to a huge backlash from the audience.
BBC News understands Mayo will not be moving to a rival broadcaster, despite some media reports suggesting he was leaving to host a breakfast show on a commercial station.
Whiley's addition to Drivetime came after Radio 2 was criticised for its lack of female presenters.
Mayo wrote on Twitter on Monday morning: "I'll continue with the (flagship) film show on 5 Live with Mark Kermode and, beyond that, other radio adventures beckon!
"But for now it's just the sadness of leaving. Radio 2 has been a wonderful place for me - my happiest radio I think. Our listeners are really quite extraordinary."
He added: "Maybe it needs to be said, maybe not but so there is no room for argument I'll be clear.
"I've loved working with the exceptional Jo Whiley and when the show was 'reconfigured ' she was my first and only choice.
One other thing. Maybe it needs to be said, maybe not but so there is no room for argument I’ll be clear. I’ve loved working with the exceptional Jo Whiley and when the show was ‘reconfigured ‘ she was my first and only choice.— Simon Mayo (@simonmayo) October 22, 2018
"Some of the abuse she has had here has been appalling. Support for a show is one thing, assaulting the dignity of a warm-hearted and loyal friend is another.
"So by all means discuss what's happening here, but let's keep some civility. Thank you. Here endeth the lesson."
Analysis by Steven McIntosh, BBC entertainment reporter
Before Jo Whiley joined Drivetime, Radio 2's daytime schedule was made up entirely of white men over 50.
While many critics acknowledged the station desperately needed more women, most argued Whiley was not the right person for the job, citing the lack of chemistry she and Mayo had.
Listeners also did not respond well - hundreds have contacted BBC News to voice their unhappiness with Drivetime in recent months.
So this was perhaps inevitable, but the timing of this announcement is interesting. It's worth noting that the latest radio listening figures (RAJARs) are due to be published later this week, which may have shown a dramatic drop-off in listeners since Whiley joined the show.
It has not yet been announced who will take over Drivetime, but the station may now take the opportunity to get more women into the daytime schedule.
As a result, we could see someone like Sara Cox, who lost out to Zoe Ball on becoming the new breakfast presenter, taking over the slot.
Whiley said: "I'm incredibly sad that Simon has decided to leave Radio 2. He's a brilliant broadcaster, a great friend and I really will miss working with him.
"However, I'm very much looking forward to hosting a new show for a new year which will have music at the very heart of it as well as guests and live sessions. Dream show, actually. Can't wait!"
Whiley's new 7-9pm weekday show will see Radio 2's evening specialist shows move slots.
A Radio 2 spokesperson said: "The Cerys Matthews Blues Show (Mon), Jamie Cullum (Tues), The Folk Show with Mark Radcliffe (Weds) and Bob Harris Country (Thurs) will all move from 8pm-9pm to 9pm-10pm.
"Radio 2 remains committed to featuring the broadcast range of music across the network."
They added that announcements about shows currently in the 9pm-10pm slot would be made in due course.
Lewis Carnie, Head of Radio 2 said: "Simon is a fantastic broadcaster, and I'd like to thank him for entertaining millions of Radio 2 listeners with his wit and warmth over the years.
"With Simon leaving, we've taken this opportunity to take a fresh look at the schedule, and create a show for Jo which will focus on her passion for music."