Yorkey was born in Omaha, Nebraska, where he was raised, before his family moved to Issaquah, Washington. He graduated from Columbia University in 1993, where he served as the Artistic Director of the Varsity Show. He is an alumnus of the BMI Lehman Engel Musical Theater Workshop.

Next to Normal was nominated for a total of eleven Tony Awards, including the Tony Award for Best Book of a Musical. The show won the 2009 Tony Award for Best Original Score, and Tony Award for Best Orchestrations. In 2010 Yorkey and Kitt were awarded the Pulitzer Prize for Drama for Next to Normal, citing “a powerful rock musical that grapples with mental illness in a suburban family and expands the scope of subject matter for musicals.”

In 2013, Yorkey’s musical with Kitt, If/Then, starring Idina Menzel, LaChanze, and Anthony Rapp, had its pre-Broadway try-out at The National Theatre in Washington, D.C. The musical subsequently opened on Broadway on March 30, 2014. The musical garnered a Tony Award nomination and Outer Critics Circle nomination for Best Original Score for Kitt and Yorkey, as well as a nomination for Best Performance by a Leading Actress for Menzel.

In 2014, Yorkey’s collaborative work, with Sting and co-librettist John Logan, The Last Ship opened on Broadway. The musical is loosely based on Sting’s album The Soul Cages (1990). It opened on September 29, 2014. Yorkey and Logan were nominated for an Outer Critics Circle Award for their book.

He wrote the music, with Kitt, for a musical version of Freaky Friday with librettist Bridget Carpenter. Freaky Friday is produced by Disney Theatrical Productions, and had its World Premiere at the Signature Theatre (Arlington, Virginia) in October 2016. The musical began performances at the La Jolla Playhouse, San Diego, on January 31, 2017 running to March 12. The cast features Emma Hunton and Heidi Blickenstaff.

Yorkey adapted Jay Asher’s bestselling novel, 13 Reasons Why, for Netflix, Paramount Television, and Anonymous Content. It was released on Netflix in March 2017.