Pro-Brexit Labour MP Kate Hoey has vowed to resist efforts to deselect her after her local party in Vauxhall passed a vote of no confidence in her.
The activists are calling on Labour to suspend her from the party and declare her ineligible to stand as a candidate.
They have accused her of "colluding" with UKIP's Nigel Farage and "propping up a failing government".
Ms Hoey, who has consistently voted with the government on Brexit, said she was "quite relaxed" about the move.
The confidence vote carries no official force within the Labour Party but local activists could hold a "trigger ballot," where sitting Labour MPs can be forced to compete for selection as a candidate against all-comers, ahead of the next general election.
Labour activists in the south London constituency are angry about Ms Hoey's support for Brexit in an area that voted strongly for Remain and for voting with the government earlier this month on an amendment to the Trade Bill, a key piece of Brexit legislation.
The no-confidence motion, which received unanimous backing at a party meeting on Thursday, says defeat in that Commons vote could have toppled the government and led to a general election that Labour was "widely expected to win".
The motion also accuses Ms Hoey of "reneging" on Labour's manifesto pledge to oppose Theresa May's approach to Brexit and of "colluding" with then UKIP leader Nigel Farage during the EU referendum campaign.
'Not a surprise'
It also attacks her backing of causes "not compatible with Labour core beliefs" such as fox hunting, "elitist grammar schools", and her chairmanship of the Countryside Alliance.
The MP, who is currently in Zimbabwe as an election observer, has represented Vauxhall since 1989.
She defended herself in a letter to local party members ahead of Thursday's vote.
"The idea there would have been a general election if Labour MPs had supported the amendment is not true," she said.
The amendment, tabled by pro-EU Tory backbenchers, "was a backhand way of staying in the customs union," she argued, and "this was not the position in the Labour manifesto on which I was re-elected".
In a statement to the Guardian, Ms Hoey said the result of the no-confidence vote was "not a surprise".
"My local party activists are solid EU Remainers," she told the newspaper.
"I will always put my country before my party and helping my constituents is a priority.
"After 29 years as an MP I am quite relaxed about the vote and it won't influence in any way how I vote in future."
Earlier this week, Shadow Chancellor John McDonnell said he was seeking to persuade Ms Hoey and three other Labour rebels to stop "propping up" the government in key Brexit votes.