In 2005, Patina Miller was one of three finalists for the role of Effie White in "Dreamgirls," which ultimately won Jennifer Hudson the Academy Award for Best Supporting Actress. In 2007, she was cast in "All My Children" and appeared in 30 episodes of the daytime soap opera. She performed in a Central Park production of "Hair" in the summer of 2008 and was featured in the musical Romantic Poetry at the Manhattan Theatre Club that fall.

Miller was cast as the lead role of Delores Van Cartier in "Sister Act," a role she had understudied for six months during its initial run in the United States, following a year-long international search.

Miller reprised the role of Deloris Van Cartier in the Broadway production of "Sister Act," which began performances on March 24, 2011, at the Broadway Theatre and officially opened April 20, 2011. Miller also made her Broadway debut in this production. For this role she won a Theatre World Award and was also nominated for the Tony Award for Best Actress in a Musical, the Outer Critics Circle Award for Outstanding Actress in a Musical, the Drama League Award for Distinguished Performance and the Drama Desk Award for Outstanding Actress in a Musical. She played her final performance in the Broadway company on March 18, 2012 and was replaced by Raven-Symoné on March 27. Miller also starred as Linda in the City Center Encores! production of "Lost in the Stars," which ran from February 3–6, 2011.

She performed as the Leading Player in the American Repertory Theater production of "Pippin" from December 5, 2012 to January 20, 2013. Miller recently reprised the role in the Broadway revival, which began performances on March 23, 2013, at the Music Box Theatre and officially opened on April 25, 2013. She won the Outer Critics Circle Award and Tony Award for Best Actress in a Musical at the 67th Tony Awards for this role.

In September 2013, it was announced that Miller will play the role of Commander Paylor in "The Hunger Games: Mockingjay." In May 2014, it was announced that she was cast as Daisy Grant, press coordinator to Elizabeth McCord (Téa Leoni) in the new CBS drama "Madam Secretary." The show premiered on Sunday, September 21, 2014, on CBS as part of the 2014–15 television season.

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