McCormack's Will Truman and Messing's Grace Adler are supporters of Clinton, though Karen Walker, played by Mullally, is firmly in the Trump camp.
Hayes' Jack McFarland is an undecided voter, and both sides try to sway him toward their candidate of choice.
"When I was as little girl, I didn't think that I could ever be president, and do you know what that was? Because no woman had ever been president of these United States," Adler said. "If you help elect Hillary Rodham Clinton, you -- just you! -- will be a part of the America that finally shattered that glass ceiling."
Add your voice to the conversation with the hashtag #VoteHoney.
Prior to the video being released, the stars teased their reunion in cryptic social media posts, below.
"Will & Grace" went off the air in 2006.