Michael Buerk delivers a preamble launching the topic, then a series of 'witnesses' – experts or other relevant people – are questioned by the panellists, who then discuss what each witness said.

The regular panellists are: Notable former panellists include Rabbi Hugo Gryn (who died in 1996), Janet Daley, Edward Pearce, Geoffrey Robertson, Michael Mansfield, politician Michael Gove, Claire Fox, Michael Portillo, Ian Hargreaves, Kenan Malik, scientist Steven Rose, philosophers Simon Blackburn and Roger Scruton, and historian David Starkey, who often attracted controversy for his blunt manner.

It moved to Wednesday evenings from 13 May 1998, in the 1998 schedule changes, with a repeat of the forty-five-minute programme on Saturday night at 10:15 pm.

Originally produced at the BBC North West's New Broadcasting House on Oxford Road in Manchester, the programme production base is Salford Quays.

In his book Bad Thoughts (US title Crimes Against Logic), libertarian philosopher Jamie Whyte, who has been a witness on the programme, advises readers to listen to The Moral Maze for innumerable examples of faulty reasoning.

Journalist and author Nick Cohen has also criticised the programme, in a piece highlighting the media careers of Trotskyite-turned-libertarian former cadres of the Revolutionary Communist Party, centred on Spiked magazine.