"If I am asked, I am there. It is not a time for procrastination, for doubts, for fears," Matteo Salvini told a rally in Florence, organised by his party to call for a "No" vote in the crucial December 4 referendum.
"There is no lack of ideas and teams, and today we start a long march. If Brexit teaches us something, if the election of Donald Trump teaches us something, (it is that) today we get going to take power," he added.
The Northern League's policy platform includes key similarities with Trump's triumphant election campaign, including economic protectionism and fighting immigration.
The Italian poll also comes as populist parties across Europe ride a wave of anti-establishment fervour driven notably by anti-immigrant sentiment, which saw Britain vote to leave the EU in June.
Italian Prime Minister Matteo Renzi has described next month's constitutional referendum as a battle between "nostalgia and the future".
The proposed reforms -- deemed the most important in Italy since World War II and already approved by parliament -- are aimed at increasing political stability in a country which has had 63 governments since 1945.
Renzi initially said he would resign if he lost the referendum, but has since backtracked, admitting that he had made "a mistake in personalising" the vote.
The "No" camp draws support from across Italy's broad political spectrum and currently enjoys a slight edge in opinion polls.