Angela Smith, MP for Penistone and Stocksbridge, joined the Lib Dems last month after sitting for three months as an independent.
She left Labour in February to join Change UK but began sitting as an independent in June.
Now, under the Lib Dem banner, Ms Smith has announced she will leave her Penisone and Stocksbridge seat and instead challenge Conservative Sir Graham Brady in his Altrincham and Sale West seat, near Manchester.
The constituency voted remain in 2016 and Sir Graham, a pro-Brexit politician, has held the seat since its creation in 1997.
Ms Smith said: “I’m delighted to be standing as the Liberal Democrat candidate in Altrincham and Sale West at the next general election, whenever that comes.
“It has been an honour to serve as the Member of Parliament for Penistone and Stocksbridge and before that Sheffield Hillsborough. Representing local people is a huge privilege and I want to thank everyone who has supported me over the years.
“We have a fantastic opportunity to beat a brexiteer MP and the Conservatives in Greater Manchester. As well as leading the fight to stop Brexit, I will stand up for the people of Altrincham and Sale West in the face of brutal Conservative cuts to our NHS, police and schools.
“Labour and the Conservatives have consistently let us down on Brexit. Only the Liberal Democrats are committed to stopping Brexit.”
An election is expected before the end of the year, and the prospective parliamentary candidates for the constituency are now Miriam Cates (Conservative), Hannah Kitching (Liberal Democrats), and John Charles Booker (Brexit Party). Labour is yet to pick a candidate but it is understood a candidate could be in place before the end of October.