She started her acting career in Chicago and won two Joseph Jefferson Awards in 2008 and 2011 for her roles as Carrie Pipperidge in Carousel[2] and Amalia Balash in She Loves Me.

She went on to receive two additional Best Actress in a Musical Tony Award nominations for her leading roles in Waitress (2016) and the Broadway revival of Carousel (2018).

She followed this with various roles in the Chicago area including Lizzie Fields in Baby, the Lady-In-Waiting in Once Upon a Mattress, and Esther Smith in Meet Me in St. Louis.

[11][12][13] In 2011, she was named Actor of the Year by the Chicago Tribune[14][15] and also was nominated for two Joseph Jefferson Awards, winning Best Lead Actress in a Musical for her performance as Amalia Balash in She Loves Me.

[16][17][18] Mueller made her Broadway debut in a revised revival of On a Clear Day You Can See Forever as Melinda Wells, a role originated by Barbara Harris.

Mueller received critical praise for her performance, with one reviewer commenting, "Her voice contains notes of Garland, but she's no diva — this is a star of supreme self-possession".

Mueller next was cast in the role of Helena Landless / Miss Janet Conover in Roundabout Theatre Company's 2012 revival of The Mystery of Edwin Drood, for which she was nominated for a Drama Desk Award.

Charles Isherwood for the New York Times noted, "But it is when Ms. Mueller tears into the musical's climactic number, 'She Used to Be Mine,' that her talents are most fully and movingly harnessed... Ms. Mueller's vibrant performance of this gentle but wrenching song, featuring a melody that soars and then recedes in waves, is the high point of the show — and for that matter a high point of the Broadway season.

[40][41] In April 2017, shortly after Mueller's departure from Waitress, it was announced that she would play the lead role of Julie Jordan in a Broadway revival of Carousel.

Miss Manners) alongside a cast including Meryl Streep, Tom Hanks, Sarah Paulson, and Carrie Coon.

[45] Also in 2017, Mueller was nominated for a Chicago/Midwest Emmy Award for her performance in the Lyric Opera's Chicago Voices concert,[46][47] which was filmed and aired on WTTW.

In early 2019, Mueller starred as Marian Paroo, opposite Norm Lewis, in the Kennedy Center's semi-staged concert production of The Music Man.

[61][62] In 2009, Mueller met and began a relationship with Andy Truschinski, an actor, film producer, and playwright, while performing opposite him in a Goodman Theatre production of A Christmas Carol.

[80] In 2016, she and partner Andy Truschinski were honored by the Alliance of Resident Theatres/New York with the Abe L. Blinder Award for Public Service and Arts Education.

[83] Mueller continues to support her own alma maters, performing at a benefit showcase for Evanston Township High School's YAMO theatre program in 2017[84] and providing opportunities for meetings and talkbacks with Syracuse University drama students.