Victoria Derbyshire (pictured), Richard Bacon and Shelagh Fogarty are leaving BBC Radio 5 Live “to explore new ventures both within the BBC and externally”.
Adrian Chiles and Peter Allen will alternately host 5 Live Daily, which will be "journalistic in tone and focus on big news stories", from October as part of the shake-up.
Chiles already hosts Friday's edition of Drivetime on the station.
BBC Sport’s Dan Walker, of Football Focus, will co-host a news programme, Afternoon Edition, with Sarah Brett from Northern Ireland’s Radio Foyle.
Both new slots will replace Bacon, Derbyshire and Fogarty’s shows.
The appointments come as the BBC is expected this month to announce the loss of around 80 jobs across its radio division – and up to 500 in BBC News.
In an email to 5 Live staff, controller Jonathan Wall said: “It's always sad to see top presenters leave, but this really is the right time to refresh. I think we have exciting times ahead…
“These changes have given me the opportunity to put together a new schedule, alongside a new line-up, and it's one that both excites me and gives me real belief that we can keep pushing 5 live forward.”
The departures of Derbyshire and Fogarty have sparked fears Radio 5 Live could be returning to the days of ‘Radio Bloke’, according to the Daily Mail.
Conservative MP Angie Bray, who is on the culture, media and sport committee, is quoted as saying: “I’m really surprised at these changes given all the BBC has said about keeping women on air.
“Victoria and Shelagh are both excellent broadcasters and will be missed.
“It does seem 5 Live is becoming more and more blokey.”
In a blog, controller Wall said: “After twenty years at 5 Live I remain as enthusiastic as ever about the station. I love it in particular because of its audience, and the new show will in essence be a conversation with that audience.”
On Derbyshire, he said: “Victoria will stay with us until September and will play a big part in our Commonwealth Games plans… We will miss both her forensic interviewing ability and her award-winning investigative journalism.”