In an interview with Italian newspaper la Repubblica, Sir Sadiq said rejoining the bloc is “inevitable” and suggested – but did not say explicitly – that the UK could rejoin without another referendum.
“I see on a daily basis the damage Brexit has done to not just London, but Londoners, the damage economically, socially and culturally,” he said, adding that US tariffs and the war in Iran have worsened the cost of living.
He said: “The facts have changed. The evidence has changed…
“I think it’s inevitable, the direction of travel at some stage we’re going to rejoin the European Union.”
A Conservative Party spokesman said: “Keir Starmer is in office but not in power.
“Ed Miliband is deciding foreign policy, Angela Rayner is deciding immigration policy, and now Sadiq Khan is deciding EU policy.
“Only Kemi Badenoch’s Conservatives are serious about cutting welfare, cutting taxes and getting Britain working again.”
Sir Sadiq also backed a rethink on parts of the government’s planned asylum crackdown, which is coming under growing pressure from some Labour MPs.
On Tuesday, Angela Rayner warned proposals to make it harder for migrants already in the UK to settle permanently were “un-British” and a “breach of trust”.
The London mayor said: “We want people, if they come here, to properly contribute, to integrate and get involved. I would hope that the Labour government would listen to myself, Angela Rayner, Andy Burnham and many others who have expressed concerns.”
On the possibility of rejoining the EU, a Reform UK spokesman said: “After the next election, Reform will reverse any attempt to drag us back into the single market and customs union.”
But Green Party leader Zack Polanski believes Brexit has been “a disaster socially, culturally, economically” and in a speech earlier on Wednesday said: “One day I do want to see us rejoin.”
He added: “Nigel Farage has chutzpah to return to the stage and say ‘things are disastrous, and I’m the person to fix it’.”
In a speech at King’s College London on Wednesday evening, former Conservative prime minister Sir John Major said Brexit had “failed to deliver its many promises” and was causing an annual loss of “£100 billion of European trade and £40 billion of tax revenue”
Sir John said Brexit was “doing enormous damage to the lives and livelihoods of the British people – and their future” and had “left the UK more solitary and vulnerable”.
“I do not believe we can fully rejoin the European Union in the near future,” he said.
“But economic wellbeing tells us we should re-build relationships with our closest neighbours as swiftly and as comprehensively as possible.”
The Liberal Democrats have been contacted for comment.