In a speech at the London Government Dinner, the mayor pointed out that the capital has some of the most deprived communities in the county and hit out at London being excluded from funding pots.
Mr Khan spoke of the success of the Elizabeth line, which had more than 60% of its contracts from outside London, as to how investment in London can help the rest of the UK.
He said: “I fear the anti-London approach could seriously exacerbate the cost of living crisis.
“Even before these latest economic shocks, too many Londoners were already finding it impossible to keep their heads above water.
“We have some of the most deprived communities in the country living here in our city.”
“To overlook London for investment – and exclude our city from various funding pots as this government has already done – is completely indefensible,” he said.
“Help for our communities should be based on need, not geography.
“A child born into poverty in Lewisham or Newham is blighted by deprivation and inequality in exactly the same way as a child born into similar circumstances in Leeds or Newcastle.”
The mayor said he wants to see ministers take bolder steps to tackle the cost of living crisis, including scrapping the benefit cap, devolving powers to freeze private rents and reverse the cuts to Universal Credit.
“More than 60% of contracts for the Elizabeth line were awarded to firms outside London,” he said.
“Tens of thousands of jobs have been created across the country because of the project. And it's estimated that it will add up to £42 billion to the UK economy as a whole.
“This isn’t a case of London monopolising investment and resources.
“This is an example of levelling-up in action – a mammoth infrastructure project that supports growth, employment and supply chains the length and breadth of our great United Kingdom.
“Indeed, just to give three examples: the trains were built in Derby, the station doors manufactured in Cheshire and the signage made on the Isle of White using steel from Dorset.”