A 63-year-old intellectual with a silver shock of hair and piercing eyes, Letwin has been waging a campaign against a chaotic "no-deal" divorce with the EU.
As parliament prepared for Saturday's crunch vote on Johnson's new pact with Brussels, Letwin pushed through an amendment effectively forcing Johnson to go back on his word and request a third extension this year.
"Despite my support for the prime minister's deal, (I) do not believe that it's responsible to put the nation at risk," Letwin told parliament.
It is not the first time Letwin, who was kicked out of the ruling Conservative party for opposing its Brexit approach, has frustrated the government.
He managed to briefly wrest control from the government over what legislation was put up for a previous vote in March, and then again last month, laying the groundwork for Saturday's delay.
The son of two Jewish-American academics, Letwin attended the elite Eton College and then the prestigious Cambridge University.
He was on prime minister Margaret Thatcher's policy unit from 1983 to 1986.
A 1985 memo, released under the 30-year rule for government documents, revealed his response to a deadly London riot, suggesting plans to support black entrepreneurs would result in the money fuelling the "disco and drug trade".
In 2015, he apologised unreservedly, saying his memo was "badly worded and wrong".
After working with the N M Rothschild investment bank, he won the safe Conservative seat of West Dorset in 1997 and has retained the southwest England constituency ever since.
A junior Conservative finance spokesman during the 2001 general election, he said he would like to cut taxes by £20 billion per year rather than the £8 billion official party line.
He became the party's interior affairs and then finance spokesman in opposition between 2001 and 2005, his main run on the front benches.
Despite his intellect, the party loyalist is prone to eye-catching gaffes.
In 2002, he let two confidence tricksters into his home at 5:15 am to use the toilet. They stole jewellery and other items.
"I am the sort of person, I suppose, who lets people use the toilet when they say they are desperate," he explained.
In 2003, he declared he would "give my right arm" to send his two children to a fee-paying school and would rather "go out on the streets and beg" than send them to the local inner London state school. He later apologised.
Close to David Cameron, Letwin helped set up the coalition government in 2010 that brought the Conservatives back into power.
As prime minister, Cameron then created the post of government policy minister especially for Letwin.
He became Cameron's problem-solver.
In 2011, Letwin was caught dumping documents about the rendition of terror suspects in a London park rubbish bin.
Cameron bumped him up to a full cabinet position in 2014, giving him overall charge of the Cabinet Office, the ministry which supports the government.
Although a convert to euroscepticism under Thatcher, he backed staying in the EU in the 2016 referendum on Britain's membership, feeling Cameron's renegotiation would keep Britain in an economic union but without the federalism espoused by some in Brussels.
Letwin returned to the backbenches when Theresa May became prime minister in the wake of the seismic vote.
But the veteran fixer is now being dubbed by colleagues a self-installed jobbing prime minister at the head of a parallel government, attempting to steer Britain through the Brexit impasse.