The party leader and sitting MEP took part in a hustings alongside other shortlisted candidates on Friday night and was revealed as the winner on Saturday morning.
The Huffington Post UK’s Owen Bennett reported this week that the candidacy would represent the biggest test of Nuttall’s leadership so far.
The by-election, triggered by the resignation of Labour MP Tristram Hunt, will be hotly contested. Ukip lost the seat by just 5,159 votes in 2015, placing second.
Labour MPs are urging the party to focus its campaign on Nuttall’s previous support for NHS privatisation.
It comes after HuffPost UK revealed that Nuttall was coming under increasing pressure from senior figures to stand in the constituency.
The by-election will be highly significant battle that 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.
Nuttall will hope he can become Ukip’s second MP with the help of Stoke’s large number of Brexit supporters, the Press Association reported.
Stoke voted 65.7% for Leave in last year’s EU referendum.
He will also be seeking to go one better than Mr Farage, who has failed in seven attempts to get elected to the House of Commons.
Addressing the local party, Nuttall said: “In the referendum last year just about 70% of voters from Stoke voted to leave the European Union.
“This was the highest vote share for Leave in any city in the United Kingdom.
“That makes Stoke the capital of Brexit.
“And be clear - nobody will fight harder than me to ensure that Brexit happens in full and good time.
“If I am elected as your MP it will send a signal to all those who are trying to put spanners in the works that their jobs are on the line.
“And in particular those Labour MPs who represent working class communities which voted Leave and now want to water down Brexit.
“They will be put on notice that if they seek to frustrate the will of the people they may as well be asking for their P45s in the post.”
Pitching himself as the anti-establishment candidate, Nuttall attacked the “metropolitan elite” at the top of the Labour Party and said he could give constituents a national voice as a party leader.
“The metropolitan elite has had the fate of working people in its grip for too long,” he said..
“It’s now time that that grip was broken.
“I have heard people say that these communities have been left behind, this is no doubt true.
“But it is a phrase that I do not like.
“I prefer to say that these communities have been let down, and let down time and time again.
“Let down by a haughty political establishment that looks down its nose at working class people, let down by a Labour Party in particular that takes their votes for granted.”