While the vote was merely symbolic, Parliament's refusal to reaffirm its support for May's approach to negotiations with the European Union represented another setback for the government as it attempts to reopen the terms of its Brexit deal with the EU.
Lawmakers voted 303 to 258 against the government's motion, which included an amendment on renegotiating the Irish backstop -- a contentious part of the deal -- along with a nonbinding amendment to prevent a no-deal Brexit.
A group of hard-line Brexiteers in May's Conservative party abstained from the vote on Thursday, unwilling to back a motion that aimed to block Britain from crashing out of Europe on March 29 without a deal.
May has previously refused to rule out a no-deal Brexit, even though a majority of lawmakers say it will plunge the UK into chaos. That is with the exception of Brexiteers, who maintain that keeping it on the table is a necessary negotiating tactic with the EU.
There is growing frustration in Brussels with May, who is seen as a less reliable negotiating partner by the day.
"She's trying appeasement but it's just not working. You would think there should be a moment she has to sacrifice party unity to ensure safe landing for her country. But [I] doubt she will, hoping eventually the EU moves in the end," one EU diplomat told CNN.
Ireland's Deputy Prime Minister Simon Coveney said Thursday night that it was Britain's responsibility to break the current impasse -- not the EU.
"We should say very firmly that the responsibility to come up with ways of solving the current impasse lies where the impasse is, which London -- not Brussels, not Dublin, not Belfast or anywhere else," Coveney told the Irish Parliamentary Foreign Affairs Committee.