Sir Keir Starmer suffered a major rebellion from his parliamentary party on Wednesday evening after 56 MPs defied a three-line whip to back an SNP amendment calling for a ceasefire in Gaza.
Eight frontbenchers, including Jess Phillips, quit the frontbench in order to back the amendment, which was rejected 293 to 125, with a majority of 168.
Among them are four shadow ministers - Ms Phillips, Yasmin Qureshi, Afzal Khan and Paula Barker - along with other frontbenchers Rachel Hopkins, Sarah Owen, Naz Shah and Andy Slaughter.
Parliamentary private secretaries Dan Carden and Mary Foy have also left their positions.
MPs voted 293 to 125, majority 168, to reject the SNP’s King’s Speech amendment calling for “all parties to agree to an immediate ceasefire” in Gaza.
But 56 Labour MPs backed the position, rejecting their party leader’s stance.
In a resignation letter, Birmingham Yardley MP Ms Phillips wrote: “This week has been one of the toughest weeks in politics since I entered Parliament.
“I have tried to do everything that I could to make it so that this was not the outcome, but it is with a heavy heart that I will be leaving my post in the Shadow Home Office team.
“On this occasion I must vote with my constituents, my head, and my heart which has felt as if it were breaking over the last four weeks with the horror of the situation in Israel and Palestine.
“I can see no route where the current military action does anything but put at risk the hope of peace and security for anyone in the region now and in the future.”
Former Labour shadow minister Naz Shah said her email inbox is full of messages from constituents who agree with her position.
She told Sky News: “We have to make our positions clear… our job in Parliament is to use our platforms to convince people, which is what I did in the chamber earlier.
“I’m not alone in calling for a ceasefire… my inbox has thousands of emails about a ceasefire. This is an issue that the British public feel strongly about.
“At some point there will be a ceasefire. Had we called for a ceasefire yesterday, 144 children might still be alive. A child dies every 10 minutes.”
The division list showed shadow ministers who supported the ceasefire amendment included Paula Barker, Rachel Hopkins, Afzal Khan, Sarah Owen, Jess Phillips, Naz Shah, Andy Slaughter, Mary Kelly Foy, Dan Carden, and Yasmin Qureshi.
The SNP tabled an amendment to the King’s Speech calling for a ceasefire which was selected for a vote by Commons Speaker Sir Lindsay Hoyle.
Labour MPs were ordered to abstain on the SNP move and have instead been told to back Sir Keir’s position calling for longer “humanitarian pauses” rather than a ceasefire.
Later on Wednesday night, shaadow science secretary Peter Kyle defended the stance taken by Sir Keir Starmer,
He said that it was “not acceptable” to back the SNP amendment.
“We have a coherent policy," he said. " Keir is leading it and it’s in step with our G7 partners. And that’s what we need to do because to have any influence in this area we’ve got to stick together as an international community.”
Labour MP John McDonnell said that Sir Keir Starmer would “not necessarily” face long-term damage from the ceasefire vote “as long as he learned lessons from it”.
Mr McDonnell said MPs should have been allowed a free vote and he did not understand the basis for Sir Keir’s position.
“I think he is going against the stream, both in terms of what people want but also the basis within the Labour Party as well,” he told ITV’s Peston programme.
Hundreds of pro-Palestine protesters shut down the main road outside the Houses of Parliament ahead of Wednesday's vote.
Huge crowds were seen in Westminster, waving flags, holding placards, and chanting 'ceasefire now'.
A Scotland Yard spokesman said: “We are on scene at a large pro-Palestinian demonstration taking place opposite the Houses of Parliament this evening. Traffic continues to flow, there are diversions in place.”
A Section 35 Dispersal Order was issued in the City of Westminster from 7.50pm, until 2am, giving officers powers to disperse people suspected of antisocial behaviour.
SNP Westminster leader Stephen Flynn said Parliament must “show moral leadership” and urged MPs to vote in favour of backing an immediate cessation of hostilities.
Liberal Democrat MP Layla Moran told the Commons on Wednesday evening that one of her family members in Gaza had died earlier in the day.
Ms Moran, the MP for Oxford West and Abingdon, said it was the “most difficult day” she had had to endure in her parliamentary career.
She told the Commons: “I wanted to let the House know that today I lost my first family member.
“The reason why this is important, having spoken about how they are in a church in Gaza City and how they didn’t I am afraid die of a bomb, instead they died perhaps for lack of food, perhaps for dehydration.
"Their health deteriorated in the last week and they couldn’t get to the hospital they needed.”