The Friends actress wore a mask to post her ballot in West Hollywood, sharing a picture of the moment to Instagram.
Aniston told her more than 35 million followers she was voting for Joe Biden and his running mate Kamala Harris, citing race, the pandemic and LGBT rights as among the key issues.
And she said it is “not funny” to vote for West, urging people to “please be responsible”.
West launched his longshot bid for the White House in July but it has been hampered by repeated failures to make the ballot in several states.
He has been asking fans to back him as a write-in candidate.
Explaining her support for Mr Biden and Ms Harris, Aniston wrote: “I voted for them because right now this country is more divided than ever.
“Right now, a few men in power are deciding what women can and can’t do with their own bodies.
“Our current president has decided that racism is a non-issue.
“He has repeatedly and publicly ignored science… too many people have died.
“I urge you to really consider who is going to be most affected by this election if we stay on the track we’re on right now… your daughters, the LGBTQ+ community, our Black brothers and sisters, the elderly with health conditions, and your future kids and grandkids (who will be tasked with saving a planet that our leadership refuses to believe is hurting).”
Aniston, best known for playing Rachel Green on Friends, said the election is not about a single issue or candidate, but “the future of this country and of the world”.⠀
The 51-year-old said: “Vote for equal human rights, for love, and for decency.”
The presidential election is scheduled for November 3.⠀