The MP for Orpington is brother to Boris Johnson, the Brexit-supporting former Foreign and Commonwealth Secretary - but, like sister Rachel, was himself a Remain supporter during Britain's referendum on European Union membership in 2016.
She expressed her admiration for her brother putting "principle ahead of party" and "country ahead of his own career" and wondered whether other MPs might follow his example.
"We've been hurtling towards a blindfolded Brexit for too long, so it's about time that politicians hand back control to the people of this country by giving them the final say on Brexit - with the option to stay and lead in Europe", said Eloise Todd of the Best for Britain anti-Brexit campaign.
Prime Minister Theresa May this week faced pressure from her Westminster allies in the Democratic Unionist Party not to allow a customs border to split Northern Ireland from the United Kingdom after Brexit.
'I've done so, if others feel that it's right for them to do so, good on them'. While Johnson's resignation is likely to spur critics in the Conservative Party, securing a second referendum would also require support from the Labour Party, which is yet to fully clarify its stance on a referendum and what that could entail in terms of the question put to the public.
A Downing Street spokesman insisted: "The referendum in 2016 was the biggest democratic exercise in this country's history".
They say that the arrangements for avoiding a hard border with the Republic of Ireland are a "humiliation" because they either tie the United Kingdom to European Union rules or split the country.
"It has become increasingly clear to me that the withdrawal agreement, which is being finalised in Brussels and Whitehall even as I write, will be a awful mistake", said Johnson, who was a transport minister in the government.
Instead, Johnson said it would be proper to give the British public a chance to vote again because of the way the Brexit negotiations have evolved. The referendum, he said, should have three choices, endorse Ms May's deal, leave without a deal, or remain in the EU.
"The Prime Minister thanks Jo Johnson for his work in Government".
The ministers have proposed that Britain continue to pay European Union membership fees up to 2021 and follow the bloc's rules to avoid a cliff edge exit when it leaves in March 2019, the Sun said.
Former BBC journalist and current University of Kent chancellor Gavin Esler said: "This - from a hugely respected minister - is an important development".
Jo Johnson, who supported Remain in the referendum campaign, delivered a stinging rebuke to Mrs May's Brexit position as he walked out of Government in protest.
An EU diplomat told Reuters earlier on Saturday that they were cautiously hopeful that an EU summit could happen in November to endorse the deal but that the volatile situation in Britain made it very hard to predict.