In 2014, Ukip were the best-supported party in the elections to the European Parliament, scooping 27 per cent of the national vote and winning 24 MEPs.
Mr Nuttall, one of those MEPs who has now taken over the reins of the party from Nigel Farage, is currently standing as Ukip's candidate in Stoke-on-Trent Central in a seat held by Labour since 1950.
Nearly 70 per cent of local voters supported Brexit at the EU referendum, at odds to Labour's pro-Brussels campaign, and Mr Nuttall revealed his championing of a "clean Brexit" was receiving a "great response" in the constituency ahead of the by-election on February 23.
Speaking to Express.co.uk at his campaign office in the Staffordshire seat, Mr Nuttall said: "We're running a professional campaign, there's big numbers on the ground and we're getting a great response."
The Ukip leader said a victory in Stoke-on-Trent Central would rank "pretty high" in the party's list of achievements over the past 23 years.
The party has previously won two by-election contests, following the defections of Tory MPs Douglas Carswell and Mark Reckless.
Asked where a Stoke-on-Trent by-election win would place, Mr Nuttall said: "Higher than two by-elections so far? Yes. Why? because they were both incumbents.
"And higher than the European elections because this is to get Ukip a foothold in Parliament.
"But it would probably just be trumped by the Brexit vote of June 23!"
Ukip leader Paul Nuttall spoke to Express.co.uk from his campaign office in Stoke-on-Trent
If I'm elected I'm a national party leader so when I stand up in the House of Commons people will listen.
Mr Nuttall claimed overturning Labour's 5,000-vote majority in Stoke-on-Trent Central would "open up a can of worms" for Jeremy Corbyn's party as other seats "could fall like dominoes" to Ukip.
The Stoke-on-Trent by-election was sparked by previous MP Tristram Hunt, a critic of Mr Corbyn, quitting Parliament in order to take a job with the V&A Museum.
A number of other Labour MPs are standing as candidates in mayoral elections later this year, meaning there could be a further exodus from Mr Corbyn's parliamentary party.
Mr Nuttall said: "We know there's going to be a series of by-elections over the summer and we will be giving it a damn good go.
"But even if we don't win [in Stoke] and we come very close, Ukip will still continue, Ukip will still campaign, Ukip will continue to grow.
"And it'll only be 12 weeks into my leadership and we will go forward confident that we will take a seat in the future."
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If elected to Parliament, Mr Nuttall outlined his "two-fold" role as an MP.
He said: "Holding the Government's feet to the fire on Brexit, ensuring it's real Brexit, and also being a national champion of the people of Stoke-on-Trent because what they've had since 1950 are Labour MPs who have been voices in the wilderness.
"Lobby fodder I think they're called in Westminster parlance.
"If I'm elected I'm a national party leader so when I stand up in the House of Commons people will listen.
"I can be their national champion and I can put Stoke-on-Trent Central on the political map."