Walz, 60, the liberal governor of Minnesota and a former high school teacher, and Vance, 40, a bestselling author and conservative firebrand US senator from Ohio, are expected to clash early and often on Tuesday night, with each trying to land a lasting blow in an event that has historically had little measurable impact on White House campaigns.
Aides to the two men predicted fireworks during the 90-minute televised debate at the CBS Broadcast Center in New York, as they defend themselves and speak up for the candidates at the top of each ticket, Democratic Vice President Kamala Harris and Republican former president Donald Trump.
Kamala Harris and Donald Trump are expected to watch the debate between JD Vance and Tim Walz. (AP PHOTO)
Walz has called his Republican opponents "weird," and Vance came under fire for past comments disparaging some Democrats as "childless cat ladies".
Harris and Trump were expected to watch the debate, and Trump said he would offer a play-by-play commentary of the event on social media.
Harris was widely viewed as the winner of her sole debate with Trump on September 10 in Philadelphia, which was watched by an estimated 67 million people.
That square-off did little to change the trajectory of an extremely close election battle. While Harris has edged ahead in national polls, most surveys show voters remain fairly evenly divided in the seven states that will decide the November election.
Political analysts say vice presidential debates can be fiery but generally do not alter the outcome of an election. That said, even a slight shift in public opinion could prove decisive with the race on a razor's edge five weeks before Election Day.
The main takeaway from the last VP debate, the 2020 encounter between then-senator Harris and then-vice president Mike Pence, was a fly that landed on Pence's head unbeknownst to Pence himself.
With no more debates planned, the stand-off allows Walz and Vance to make closing arguments on behalf of their campaigns - just as early voting ramps up across the country.