Change UK has lost six of its 11 MPs following a disappointing performance in last month's EU elections, when it failed to get a single MEP elected.
The party announced that a new party leader, Anna Soubry, had been elected.
She said she was "deeply disappointed" that Heidi Allen, Chuka Umunna, Sarah Wollaston, Angela Smith, Luciana Berger and Gavin Shuker had left.
The departing MPs said they would be "returning to supporting each other as an independent grouping of MPs".
Change UK - formerly known as the Independent Group - was formed earlier this year by MPs who quit Labour and the Conservatives.
It pledged to push for any Brexit deal negotiated by the government to be voted on at a referendum - or "People's Vote" - in which it would campaign for the UK to remain in the EU.
But in last month's European Parliament elections, it gained only 3.4% of the vote.
A joint statement from the six outgoing members said their priority was now "to provide collegiate leadership to bring people together in the national interest".
"We know the landscape will continue to shift within the political environment and have concluded that by returning to sit as independents, we will be best placed to work cross-party and respond flexibly.
"We wish our colleagues well as they continue to build Change UK."
In a personal statement, former Labour MP Mr Umunna called for the "Remain forces" in Parliament to "work even more closely together", especially at the next general election, and urged them to "regroup and consolidate activity to maximise our impact".
"The movement built around Change UK has an important role to play in this," said Mr Umunna. "However, whilst I believe it should carry on as an organisation, I do not believe Change UK should carry on in its current form.
"This has put me in a fundamentally different place not only to other Change UK parliamentary colleagues, but also its activists and candidates who should be free to take the party in the direction they wish."
'Roll up our sleeves'
Former Conservative Ms Soubry, who has taken over from Ms Allen as leader, said she was disappointed the split had come "at such a crucial time in British politics".
"Now is not the time to walk away, but instead to roll up our sleeves and stand up for the sensible mainstream centre ground which is unrepresented in British politics today."
She said the party was "as determined to fix Britain's broken politics as we were when we left our former parties".
BBC political correspondent Ben Wright said there had "clearly been turmoil in the party's ranks for number of weeks".
"It has been obvious that there was an internal disagreement over where the party should be positioning itself, what its long term tactics should be, whether it should be cosying up to the Lib Dems or maintaining itself as an independent party," he said.
"Change UK was being squeezed by the other parties campaigning for Remain and didn't keep the momentum going that it had earlier in the year when it launched."
Changing the established broken politics was never going to be easy. But I’m determined to stand up with #ChangeUK and fight for the mainstream centre ground values that led me to leave @UKLabour only a few months ago. I’m proud of our achievements & I’m in it for the long haul.— Chris Leslie (@ChrisLeslieMP) June 4, 2019
After the split was announced, Change UK sent an email to members, appealing for their "help and support going forward".
It added: "While British politics slips into chaos around us, now is the time to stand firm in our beliefs and champion the mainstream centre ground values we articulated when we left our former parties in the first place."
'Door is open'
The outgoing leader of the Liberal Democrats, Sir Vince Cable, said it was "not at all surprising" that the party had split, but his "door was always open" if they wanted to join his instead.
He told the BBC he had heard "rumours" and it would be "ideal" if the departing MPs became Lib Dems, but said: "I don't want to comment on that before there is any official announcement."
Sir Vince added: "I don't want to gloat over their failure. It was a failure, but we have got to move on and I want to be positive about it.
"I am simply acknowledging the fact they have tried this project, they are brave people, they broke away from their parties and they deserve credit for that, but setting up a new centre party in the British centre doesn't work."