In chronicling his journey from a difficult childhood to the US Marines, Yale Law School, venture capitalism and finally the Senate, Vance, 39, introduced himself to Americans while using his story to argue that he understands their everyday struggles.
"I grew up in Middletown, Ohio, a small town where people spoke their minds, built with their hands and loved their God, their family, their community and their country with their whole hearts," Vance said at the Republican National Convention in Milwaukee.
"But it was also a place that had been cast aside and forgotten by America's ruling class in Washington."
"Career politicians" like President Joe Biden, Vance said, were responsible for trade policies and foreign wars that hurt communities like his.
"President Trump's vision is simple - we won't cater to Wall Street, we'll commit to the working man," he was due to say, according to excerpts released ahead of time.
"We won't import foreign labour, we'll fight for American citizens."
In a sign of his potential value to the ticket, he also planned to speak directly to the working and middle classes in Michigan, Pennsylvania and Wisconsin - three Rust Belt swing states likely to decide the November 5 election.
Vance will acknowledge his mother Beverly, a single mother who struggled with money and addiction.
"I am proud to say that tonight my mom is here, 10 years clean and sober," Vance will say, according to the excerpts.
Vance's youth and populism have him well-positioned to carry Trump's Make America Great Again movement beyond a potential second Trump term.
His prime-time debut, less than two years after assuming his first public office, caps a meteoric rise and a transformation from a fierce Trump critic to one of his most loyal defenders.
Author of the bestselling memoir Hillbilly Elegy, he has helped to shape Trump's populist instincts into a policy agenda that would pull the US back from its dominant role in global affairs.
Vance has opposed military aid for Ukraine and defended Trump's attempts to overturn his 2020 election loss to Biden. At half Trump's age, Vance potentially has decades ahead of him to influence the Republican Party.
He has argued the government must do more to assist the working class by restricting imports, raising the minimum wage and cracking down on corporate largesse.
Those positions, at odds with the Republican Party's traditional pro-business stance, nonetheless track Trump's program closely.
Biden was forced off the campaign trail on Wednesday after testing positive for COVID-19.
The illness capped three tumultuous weeks in which Biden has struggled to assuage panicked Democrats that he can still defeat Trump in the election following a poor debate performance on June 27.
Trump, his right ear still bandaged after it was grazed by a would-be assassin's bullet at a Saturday rally in Pennsylvania, walked into the convention to roars for the third straight night, with James Brown's It's a Man's Man's Man's World playing throughout the arena.
He shook hands with Texas Governor Greg Abbott and Florida Senator Marco Rubio in the VIP box and pumped his fist in the air, mouthing "thank you" to the crowd.
The evening featured a hard-hitting, emotional video in which families of soldiers killed during the 2021 US troop withdrawal from Afghanistan blamed Biden for their deaths.
The relatives then took the stage and voiced their anger, with some delegates wiping away tears.
Several speakers also levelled aggressive and sometimes baseless attacks against the Biden administration.
Former Trump White House official Peter Navarro, who was released from prison earlier in the day after serving four months for contempt of Congress, received a huge ovation as he took the stage on Wednesday.