[4][9] He attended Midwood High School in Brooklyn, and graduated from Princeton University in 1995 with a BA in English after completing a 116-page long senior thesis, titled "Doubling and the Identity Construct in Charlotte Perkins Gilman's 'The Yellow Wallpaper,' Jean Rhys's Wide Sargasso Sea, and Charlotte Bronte's Jane Eyre", under the supervision of Gina Dent.

After appearing in a few minor television roles, he moved on to co-star in the 2003 film The Human Stain, playing the younger version of the Anthony Hopkins character, Coleman Silk.

Miller worked extensively on the role, not only in researching Anthony Hopkins, but by embarking on a four-month regimen to accurately portray Silk as a boxer.

He played the role of a gifted structural engineer who created an elaborate scheme to help his brother, Lincoln Burrows (Dominic Purcell), escape death row after being found guilty of a crime he did not commit.

Covering both the front of Miller's torso and his back, along with both arms from shoulders to wrists, the special effects for the tattoo took over four hours to apply.

[25] In July 2014, it was announced that Miller had joined the cast of The CW superhero series The Flash in a recurring role as Leonard Snart / Captain Cold.

Miller exited Legends of Tomorrow as a series regular at the end of season one, but signed a contract with Warner Bros. TV to continue portraying Snart simultaneously on multiple shows in the Arrowverse.

[30] He is reportedly in negotiations to write the screenplay adaptation of the novel The Story of Edgar Sawtelle by David Wroblewski which is set to be produced by Oprah Winfrey and Tom Hanks among others.

[31] Miller came out as gay in 2013, and in 2020 announced that he was no longer interested in portraying straight characters in film or television, and thus would not participate in a sixth season of Prison Break if it were produced.

[33] In 2024, it was reported that Miller will reunite with his Prison Break co-star, Dominic Purcell, for a new hostage recovery drama called Snatchback.

[35] However, he came out as gay in August 2013, when he posted a letter on GLAAD's website declining an invitation to attend the Saint Petersburg International Film Festival because he felt "deeply troubled" by the Russian government's treatment of its gay citizens (referring to the Russian LGBT propaganda law, enacted the previous June, which banned "propaganda of nontraditional sexual relations").

[36][37] Miller wrote that he "cannot in good conscience participate in a celebratory occasion hosted by a country where people like myself are being systematically denied their basic right to live and love openly".

[36] At the 2013 Human Rights Campaign Dinner in Seattle, Washington, Miller said he had attempted suicide multiple times as a teenager before coming out as gay.

"[38] He discussed struggling in Hollywood as a closeted actor, and talked about how his involvement in the ManKind Project helped him learn about brotherhood, sisterhood, and being part of a community.