Sir Keir Starmer will face the first major ballot box test of his leadership on May 6 after a by-election was formally triggered.
Labour chief whip Nick Brown moved the writ at the start of business in the Commons on Thursday to initiate the contest for Hartlepool.
It is a seat long held by Labour and the party fought off a strong Conservative and Brexit Party challenge at the 2019 general election, although their majority was reduced to just under 3,600, down from 7,650 in 2017.
The contest will be the first parliamentary by-election held since Sir Keir took over from Jeremy Corbyn last year.
By-elections take place between 21 and 27 working days from the issuing of a writ.
Labour confirmed this means the Hartlepool contest will be on May 6.
Mike Hill resigned as MP for the north east constituency earlier this month.
He was suspended by Labour in September 2019 over allegations he sexually harassed a woman, but had the whip restored to contest the general election two months later.
According to The Sunday Times, Mr Hill claimed £2,000 on parliamentary expenses for the excess on his employment liability policy as he looked to fight the allegations.
SNP chief whip Owen Thompson also asked for the writ to be issued on April 6 to enable a by-election in the constituency of Airdrie and Shotts.
Neil Gray resigned ahead of his bid to represent the same area at the Scottish Parliament in the May election.
The SNP member made his final speech at Westminster on Tuesday, explaining a desire to be closer to home had driven his decision.