In 1993 he returned to Brigham Young University to premier his play In the Company of Men, for which he received an award from the Association for Mormon Letters. He taught drama and film at IPFW in Fort Wayne, Indiana in the early 1990s where he adapted and filmed the play, shot over two weeks and costing $25,000, beginning his career as a film director. The film won the Filmmakers Trophy at the Sundance Film Festival, and major awards and nominations at the Deauville Film Festival, the Independent Spirit Awards, the Thessaloniki Film Festival, the Society of Texas Film Critics Awards and the New York Film Critics Circle.
LaBute has received high praise from critics for his edgy and unsettling portrayals of human relationships. In the Company of Men portrays two misogynist businessmen (one played by Eckhart) cruelly plotting to romance and emotionally destroy a deaf woman. His next film Your Friends & Neighbors (1998), with an ensemble cast including Eckhart and Ben Stiller, was a shockingly honest portrayal of the sex lives of three suburban couples. In 2000 he wrote and directed an off-Broadway play entitled Bash: Latter-Day Plays, a set of three short plays depicting essentially good Latter-day Saints doing disturbing and violent things. One of the plays was a much-talked-about one-person performance by Calista Flockhart. This play resulted in his disfellowship (a softer form of discipline that does not remove the member from the membership rolls, unlike excommunication) from the LDS Church. He has since formally left the church .
LaBute's 2002 play The Mercy Seat was one of the first major theatrical responses to the September 11, 2001 attacks. Set on September 12, it concerns a man who worked at the World Trade Center but was away from the office during the attack — with his mistress. Expecting that his family believes that he was killed in the towers' collapse, he contemplates using the tragedy to run away and start a new life with his lover. Starring Liev Schreiber and Sigourney Weaver, the play was a commercial and critical success, due in large part to its willingness to confront the myths that many New Yorkers had constructed to console themselves in the aftermath of the attacks.
LaBute's latest film is The Wicker Man, an American version of a British cult classic. His first horror film, it starred Nicolas Cage and Ellen Burstyn and was released on September 1, 2006 by Warner Bros. Pictures to scathing critical reviews and mediocre box office. His latest play to open in the US, Wrecks, starring Ed Harris, opened to excellent reviews, and an extended, sold out run at the Public Theater in New York City, in October, 2006. He is working with producer Gail Mutrux on the screen adaptation of The Danish Girl by David Ebershoff. Neil is also a Jury Memeber of the on going Filmaka short film contest.