Epstein was born in Toronto, Ontario. His mother, Kathy Kacer, is a Norma Fleck Award-winning Writer of children's stories about the Holocaust, and his father, Ian Epstein (born 1955), is a Lawyer. He has an older sister, Gabi, an Actress and jazz singer. Epstein is Jewish and was raised in Conservative Judaism.

Also in 2009, Epstein starred as CB (a.k.a. Charlie Brown) in Dog Sees God: Confessions of a Teenage Blockhead, described as a "comedic deconstruction of the famous Peanuts characters." In this production, CB copes with the recent death of his beagle and discovers that he is in love with Beethoven (a.k.a. Schroeder). Theatre critic Richard Ouzounian wrote, "Jake Epstein is brilliant as CB, a bunch of nerve endings searching for a place to settle. Epstein is so beautifully open and honest that you go with him on every step of his journey."

He played Will in Green Day's Tony-winning rock musical American Idiot during the 2011-2012 North American tour. Epstein said, "I always think of American Idiot as my generation's The Who's Tommy or Pink Floyd's The Wall. American Idiot was very much like that time in the world, right after Sept. 11th...It was like a time of not knowing what to feel and that's what spawned this show."

Epstein made his Broadway debut in Spider-Man: Turn Off the Dark as the alternate for lead role Peter Parker/Spider-Man. He joined the company on December 4, 2012, and performed Saturday and Sunday matinees, with his first show having taken place on December 8 at the Foxwoods Theatre. Epstein referred to the role as a "childhood fantasy come true." He played his final performance on August 12, 2013, to begin rehearsing for a new musical titled Beautiful: The Carole King Musical, which opened on Broadway on January 12, 2014. This marked his second Broadway show in less than a year. The musical was based on Carole King's life, and Epstein portrayed her former husband Gerry Goffin. He indicated that it was not easy playing the man who broke King's heart. Epstein said, "I'm trying to make his struggle clear, so people understand why he did the things he did. He's not just a villain. I hope people see it's more complicated than that." He remained with the cast until September 21, 2014.

Epstein made his professional stage debut in a Soulpepper Theatre Company production of Our Town at the Royal Alexandra Theatre before playing the Artful Dodger in Mirvish Productions' stage production of Oliver! After appearing on the TV show The Zack Files, he played Craig Manning on Degrassi: The Next Generation for five seasons and won the Gemini Award. The character of Craig became a musician on the show and had to cope with parent abuse and bipolar disorder. Epstein said, "At the time, mental illness was not really something anyone was talking about. There was a huge stigma attached — I had never seen [bipolar disorder] on TV, and certainly not in a teenager. I loved the opportunity to portray someone who was conflicted and not perfect..." Craig impregnated a girl named Manny who gets an abortion, and Epstein noted that those episodes were "initially banned" in the United States. Epstein indicated that he "got the chance to really flesh out this guy that felt like a darker extension of me."

In 2016 Epstein starred as a closeted gay man in the off-Broadway show Straight. He spoke about the script, "What resonated with me is how a straight person is just a person, but a gay person is a gay person—it’s part of the title you give somebody...I thought the whole angle that the play takes about not a fear of coming out but a fear of definition, a fear of being labeled as a gay man, was an argument that’s not really made in our sort of post-acceptance society. It’s not about a guy who’s afraid of coming out; it’s about a guy who’s not connected with quote-unquote ‘gay culture.’" Critic Michael Glitz described Epstein's performance as "immensely appealing" and wrote that the three-member cast "elevated the show considerably with their charm and chemistry, led by Epstein’s increasingly substantial stage chops." New York Times critic Andy Webster wrote, "Mr. Epstein ably embodies a vaguely passive-aggressive, noncommittal male archetype."