UKIP leader Paul Nuttall will stand in the Stoke-on-Trent Central by-election on 23 February, the party has said.
A by-election was triggered earlier this month when Labour MP Tristram Hunt quit to become the director of London’s Victoria and Albert Museum.
The seat is traditionally a safe Labour one, but it will be a significant battle for the party as its majority has fallen in recent polls.
Labour is due to choose its candidate on Wednesday.
Stoke-on-Trent recorded one of the highest proportion of Leave votes anywhere in the UK in last summer’s EU referendum at just under 70%, despite Labour’s policy being to back Remain.
Before the referendum, Labour had seen its majority in Stoke Central fall from 20,000 in the 1997 general election to about 5,000 in 2015.
Mr Nuttall’s decision to stand indicates UKIP’s belief that it has a strong chance of taking the former Labour stronghold.
The by-election is likely to shed light on UKIP’s level of support after Nigel Farage’s leadership, the shape of post-Brexit politics in England and Jeremy Corbyn’s performance as opposition leader.
Mr Nuttall will hope he can become UKIP’s second MP.
The by-election will be held alongside a separate poll in the Cumbrian seat of Copeland, triggered by the resignation of another leading Labour MP, Jamie Reed.
Labour has selected former hospital doctor Gillian Troughton to stand in Copeland.
Labour’s majority over the Conservative Party was cut to 2,564 votes at the last general election.
Mr Reed, a persistent critic of Labour leader Jeremy Corbyn, announced that he was standing down as an MP to take up a position at the Sellafield nuclear power plant.
UKIP has chosen Fiona Mills, a pro-nuclear power candidate who works in the NHS, to fight the Copeland by-election.