Groff starred as Patrick Murray, a gay video game developer, in HBO's comedy-drama series Looking. On March 23, 2015, HBO cancelled Looking after its second season but greenlit a television film to conclude the story. In April 2013, Groff joined another HBO production, playing Craig Donner in the film adaptation of Larry Kramer's play The Normal Heart. He returned to the London stage on May 19, 2015, to star in a one-night-only concert of the musical How to Succeed in Business Without Really Trying, at the Royal Festival Hall.
Groff starred in a production of the musical A New Brain, presented as part of the New York City Center's Encores! Off-Center staged concert series. The show was directed by James Lapine and took place from June 24 through June 27, 2015. On March 3, 2015, he joined the cast of the musical Hamilton, replacing Brian d'Arcy James in the role of King George III. He held the role for the remainder of the show's off-Broadway production, through May 3, 2015. He also appeared in as King George III in Hamilton which was added to Disney+ on July 3, 2020. He reprised the role in the Broadway production, which started performances July 13, 2015. Groff, along with the rest of the cast, won a Grammy Award for Best Musical Theater Album for appearing as a featured performer on the original Broadway cast recording. He was also nominated for the Tony Award for Best Featured Actor in a Musical.
In April 2015, Groff was honored by the Point Foundation with the Point Horizon Award honoring a "trailblazer who has taken a leadership role as an advocate" of LGBTQ communities. In December 2015, he was honored by Equality Pennsylvania with the Bayard Rustin Award, which "recognizes a Pennsylvanian who is continuing the work to ensure that the LGBT community will be visible, accepted, and celebrated in our society."