The 40-minute interview was taped Tuesday at the White House in the Roosevelt Room.
"Anyone who sits on the sidelines or makes a protest vote is a vote for Trump," Obama said, "and that would be badly damaging to this country, and damaging for the world."
The president continued, "The stakes are high. The choice in this election should be really clear. Every single issue we’ve made progress on in the last eight years is going to be on the ballot."
Obama also addressed the rise of Trump as it relates to the perception by some voters that both major political parties ignore the white working class.
"This whole conversation that’s been had lately in the aftermath of the rise of Trump, it's this notion that part of what's happened is that both Republican and Democratic elites have neglected the white working class," he told Maher.
Maher also raised a pet issue of his, the legalization of marijuana. Obama acknowledged a need for "a more serious conversation about how we're treating marijuana and our drug laws in general."
The president also addressed his concerns about the media, particularly what he calls, its "Balkanization."
"The question I have when it comes to the media is how do we create a space where truth gets eyeballs and is entertaining and we can build a common conversation," he said. "When I leave here, one of the things I'm most concerned about is the Balkanization of the media, where you’ve got 800 stations, you've got all these websites, and people have difficulty just sorting out what’s true and what's not."
He added, "If you don't have some common baseline of facts ... it's very hard to figure out how we move democracy forward ... If I watched Fox News, I wouldn't vote for me either."