Dominic Cummings has accused the Health Secretary of "criminal, disgraceful" interference with the Test and Trace scheme to meet a "stupid" testing target.
The former No10 adviser repeatedly said Matt Hancock should have been fired for his conduct during the pandemic - and claimed the testing scheme had to be effectively taken off him.
Mr Cummings claimed Boris Johnson came close to sacking Mr Hancock in April but he eventually refused to dismiss him.
In an explosive Commons hearing, Mr Cummings sought to pass blame onto the Health Secretary for the delays in setting up the Test and Trace scheme, which wasn't established until May last year.
He also pointed to Boris Johnson's hospitalisation with Covid-19 in April, saying the "whole core of Government fundamentally fell apart".
Mr Hancock made the ambitious pledge to deliver 100,000 tests a day by May 2020, which was met just in time.
But a row erupted at the time over how the tests had been counted as tens of thousands were at-home tests which had been delivered, but hadn't yet been returned.
Mr Cummings told MPs: "In my opinion, disastrously, the Secretary of State [Matt Hancock] had made - while the PM was on his near deathbed - this pledge to do 100,000 [tests a day] by the end of April.
"This was an incredibly stupid thing to do because we already that goal internally."
When he returned to work after having Covid himself, Mr Cummings said he started receiving calls from people who said "Hancock is interfering with the building of the Test and Trace system because he's telling everybody what to do to maximise his chances of hitting his stupid target by the end of the month".
He said: "We had half the Government, with me in No10, calling round frantically saying, 'Do not do what Hancock says, build the thing properly for the medium term'.
"And we had Hancock calling them all saying 'down tools on this, do this, hold tests back so I can hit my target.'
"In my opinion he should've been fired for that thing alone, and that itself meant the whole of April was hugely disrupted by different parts of Whitehall fundamentally trying to operate in different ways completely because Hancock wanted to be able to go on TV and say 'look at me and my 100k target'.
"It was criminal, disgraceful behaviour that caused serious harm."
He claimed a fresh agency was set up to handle Test and Trace due to Mr Hancock's conduct as he lashed out at "bureaucratic infighting".
Mr Cummings said he warned the PM that "if we don't fire the Secretary of State and we don't get the testing in someone else's hands, we are going to kill people and it will be a catastrophe".
He said there was "constant, repeated lying" about PPE during the pandemic.
He said this could be backed up by then Cabinet Secretary Mark Sedwill, who he said told Boris Johnson "the British system is not set up to deal with a Secretary of State who repeatedly lies in meetings".
Mr Hunt said they were "very serious allegations said under parliamentary privilege" and urged Mr Cummings to provide evidence of his claims before Mr Hancock appeared in front of MPs in a fortnight.
Downing Street did not deny that the Prime Minister considered sacking Mr Hancock last April but insisted the PM has confidence in the Health Secretary now.
Asked if Mr Johnson still has confidence in the Health Secretary, the Prime Minister's official spokesman said: "Yes, the Health Secretary has been working closely with the Prime Minister throughout and has been fully focused on protecting the health and care system and saving lives."
A spokesman for Mr Hancock said: "At all times throughout this pandemic the Secretary of State for Health and Social Care and everyone in DHSC has worked incredibly hard in unprecedented circumstances to protect the NHS and save lives.
"We absolutely reject Mr Cummings' claims about the Health Secretary.
"The Health Secretary will continue to work closely with the Prime Minister to deliver the vaccine rollout, tackle the risks posed by variants and support the NHS and social care sector to recover from this pandemic."
Mr Hancock is expected to lead a Downing Street press conference on Thursday.
