In the Company of Men portrays two 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, earned an R-rating for its portrayal of the sex lives of three yuppie couples in the big city.

[11] In 2001, LaBute wrote and directed the play The Shape of Things, which premièred in London, featuring film actors Paul Rudd and Rachel Weisz.

Set in a small university town in the American Midwest, it focuses on four young students who become emotionally and romantically involved with each other, questioning the nature of art and the lengths to which people will go for love.

She even pretends to fall in love with him, prompting an offer of marriage, whereupon she cruelly exposes and humiliates him before an audience, announcing that he has simply been an "art project" for her MFA thesis.

In 2001, LaBute and producer Gail Mutrux founded the Pretty Pictures firm, with a first-look deal at USA Films.

[13][14] Set on September 12, it concerns a man who worked at the World Trade Center but was away from the office during the infamous 2001 terrorist 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.

[15] While hesitant to term The Mercy Seat "political theater", Labute said, "I refer to this play in the printed introduction as a kind of emotional terrorism that we wage on those we profess to love."

LaBute framed the classic play in overtly metatheatrical terms, adding a lesbian romance subplot.

Originally when it premiered in New York City at the Westside Dance Project, "[legend] has it ... that one unimpressed member of the audience shouted: "Kill the playwright!""

[19] The Break of Noon premiered Off-Broadway at the Lucille Lortel Theatre in an MCC Theater production on October 28, 2010 (previews), running to December 22, 2010.

[23] The Way We Get By opened Off-Broadway at the Second Stage Theatre on May 19, 2015, starring Amanda Seyfried and Thomas Sadoski, with direction by Leigh Silverman.

In an interview with Screen Comment's Sam Weisberg, he said: "I have had a lot of people direct my material for the theater, but I haven't had anyone do my work on film.

[29] In February 2018, MCC Theater terminated its relationship with him ending his place as their playwright-in-residence and their plans to produce his next play Reasons to Be Pretty Happy in the summer.

[38] Citing the misanthropic tone of the plot in the films In the Company of Men, Your Friends & Neighbors and The Shape of Things, film critic Daniel Kimmel identified a pattern running through LaBute's work of being that the unlikeable, main antagonists of those three films end up getting away with their lying, scheming and mis-deeds, coming out on top of all the other characters as the real winners of those stories by quoting: "Neil LaBute is a misanthrope who assumes that only callous and evil people, who use and abuse others, can survive in this world."

LaBute even shares some similar themes with Mamet including gender relations, political correctness, and masculinity.