In 2007, Mayer won his first Tony Award for his direction of the musical adaptation of Spring Awakening (2006), which also took the award for Best Musical. He was nominated for the 2002 Tony for his direction of Thoroughly Modern Millie, which he then directed on London's West End. Mayer also won the Drama Desk Award for Outstanding Director of a Musical for both Spring Awakening and Thoroughly Modern Millie.
Other Broadway credits include The Lion in Winter (1999), the 1999 revival of You're a Good Man, Charlie Brown, Side Man (1998; Drama Desk Award), the 1998 Tony Award-winning revival of Arthur Miller's A View from the Bridge starring Anthony LaPaglia and Brittany Murphy, for which he was nominated for a Tony and won the Drama Desk Award, and Triumph of Love, the musical starring Betty Buckley, Susan Egan and F. Murray Abraham, with music by Jeffrey Stock and lyrics by Susan Bikenhead. He worked on American Idiot the musical, based on Green Day's 2004 album American Idiot and the 2011 revival of On a Clear Day You Can See Forever starring Harry Connick, Jr.. He most recently directed the first Broadway production of Hedwig and the Angry Inch, which opened in 2014.
Mayer's off-Broadway directing credits include The Credeaux Canvas, John C. Russell's Stupid Kids, Peter Hedges' Baby Anger, Theresa Rebeck's View of the Dome, and the New York premiere of Janusz Głowacki's Antigone in New York.
After directing on- and off-Broadway for more than 15 years, Mayer made his feature film directorial debut with A Home at the End of the World, starring Colin Farrell andRobin Wright Penn, in 2004. He went on to make the family film Flicka (2006), an adaptation of the story My Friend Flicka, which became a hit in DVD market. In 2013 and 2014 he directed selected episodes of Amazon's Alpha House starring John Goodman. In 2015, he directed a new film adaptation of The Seagull, starring Annette Bening,Corey Stoll, Saoirse Ronan. He directed the pilot of NBC's TV series Smash.