Pence, the Republican governor of Indiana, attempted to paint Hillary Clinton as symbolic of "the status quo," while Democratic Virginia Senator Tim Kaine frequently challenged him to defend the statements of running mate Donald Trump has made throughout the campaign.
Both accused the other of running a more insulting campaign during a showdown at Longwood University that was characterized by frequent interruptions.
Pence at times seemed unwilling or unable to fully explain his opponent’s words.
"He's not a polished politician like you and Hillary Clinton," Pence conceded as Kaine questioned him about Trump's past comments on abortion.
Kaine spent most of the night bringing up Trump's now notorious comments on Mexicans, praise of Russian leader Vladimir Putin and a number of Trump's other most incendiary comments.
"Six times I've asked you to defend your running mate," Kaine said about an hour into the debate. "Six times you've refused to do so. He's asking people to vote for somebody he cannot defend."
"I am very, very happy to defend Donald Trump," Pence countered.
The Republican spent the sparring match charging that Clinton is running an "insults driven campaign," citing her recent comments that half of Trump's supporters belong to a basket of deplorables.
At multiple times throughout the 90-minute debate, Kaine also attempted to hit Pence for Trump's refusal to release his tax returns and a recent New York Times report that found he may have avoided paying taxes for 18 years.
Just 31 percent of the country sees Clinton as more "honest and straightforward" than Trump, according to an NBC/Wall Street Journal poll released last month. The same survey found just 23 percent of respondents think Trump has the "right temperament" to be commander-in-chief.