Plaid Cymru has done a deal with the Lib Dems to not field a candidate in the Brecon and Radnorshire by-election and instead endorse Lib Dem candidate Jane Dodds.
Plaid's leader Adam Price signalled this could be the start of "a wider vision of having a remain alliance".
The Green Party had already said it will not field a candidate to "maximise the chances" of the remain-backing candidate beating the Conservative Party and the threat of the Brexit Party.
Conservative MP Chris Davies lost his seat after a recall petition was triggered in the wake of a criminal conviction over his expenses.
More than 10,000 people living in the constituency, just under one in five voters, said they no longer wanted him to be their MP.
Vince Cable, the outgoing Lib Dem leader in Westminster, and Adam Price announced the pact in Westminster on Thursday and spoke of a "more mature" politics.
Sir Vince said that it was a "welcome development that two of the strongest remain parties in Wales are going to work together for the wider remain cause".
Mr Price said he could not force Plaid voters to go out and vote for the Lib Dem candidate, but that they had to look to the bigger picture and back a remain candidate.
He said: "We can't command our supporters to turn up and vote for another political party but I think we can signal that in our considered view, from our perspective of the Welsh national interest and our cause, which is independence within the European Union for Wales in the future, at this time the best way we can continue to those goals is to elect an MP at this by-election which is a member which supports Wales remaining the European Union".
However, he admitted he didn't think all members would agree with the stance. Sir Vince said he "would like to see this enshrined in a much wider remain alliance".
"It's the right thing for us to do, anyway, but I think the fact we're able to do it in the context of a wider agreement to explore other co-operation is very encouraging because it allows us a means of changing the political landscape in Wales."
He said it "shouldn't be underestimated how big this is. Political parties are tribal and don't like working together".
Asked where he thought his party's biggest threat came from, Sir Vince said The Brexit Party was a "significant threat" and "proving to be very active. We're certainly aware of the threat".
But he said their election in Brecon and Radnorshire would be "bad for the country".
He also said Labour should have joined into the agreement between remain-supporting parties. "They have sat on the fence for three years," he said.
