After graduating from Wesleyan University, Kail became assistant stage manager at New Jersey's American Stage Company. Kail directed the 24 Hour Plays benefit performances in 2007 and 2008, where "6 short plays are written, rehearsed, directed, and performed in 24 hours." In 2007, he directed Julia Jordan's A Bus Stop Play, and Beau Willimon's Zusammenbruch in 2008. Both shows played at the American Airlines Theatre on Broadway. Kail directed the hit Broadway musicalIn the Heights, which garnered him a Tony Award nomination for Best Direction of a Musical. The musical premiered on Broadway, starting in previews on February 14, 2008, with an official opening on March 9, 2008, at the Richard Rodgers Theatre. Kail directed Broke-ology, which played from October 5, 2009, to November 22, 2009, at the Lincoln Center Theater Off-Broadway. This play garnered Kail an AUDELCO Award nomination for Best Director of a Dramatic Production. Kail also staged the world premiere at the Williamstown Theatre Festival. Also in 2009, Kail directed the New York City Center's Encores! production of the musical The Wiz. Kail directed Eric Simonson's play Lombardi, based on Green Bay Packers coach Vince Lombardi through a week in the 1965 season, as he attempts to lead his team to the championship. Lombardi officially premiered on Broadway at the Circle in the Square Theatre on October 21, 2010. He then directed the Off-Broadway run of Nathan Louis Jackson's When I Come to Die, which ran in January and February 2011. Kail reunited with Lombardi playwright Eric Simonson on Magic/Bird, a new play chronicling the intertwined life stories of basketball Hall of FamersLarry Bird and Earvin "Magic" Johnson. The play premiered on Broadway at the Longacre Theatre on March 21, 2012, in previews, officially on April 11, 2012, and closed on May 12, 2012. Kail directed, with the cast that featured Kevin Daniels as "Magic" Johnson and Tug Coker as Larry Bird. Kail continued his collaboration with Lin-Manuel Miranda, directing the musical Hamilton in 2015, both Off-Broadway and on Broadway, for which he won a Tony Award. Kail directed for Paramount Television, screened live on Fox on January 31, 2016; the world premiere of Dry Powder with Hank Azaria, Claire Danes, John Krasinski and Sanjit De Silva which ran from March to May 2016 at The PublicTheater in New York City; and Tiny Beautiful Things, also at The Public, from November to December 2016.