He is also known for his roles in another two of Twin Peaks co-creator David Lynch's films: Paul Atreides in Dune (1984) and Jeffrey Beaumont in Blue Velvet (1986).

[3] His mother, Catherine (née Stone;[4] 1934–1986),[5] was a public relations director for a school district[6][7] and a homemaker who was active in community arts programs.

[8][10][14] MacLachlan was introduced to stage acting by his mother when she became director of a youth theater program for teenagers that she helped set up in Yakima.

[6][8] In his senior year, he had the lead role of Brindsley Miller in a production of Peter Shaffer's one-act play Black Comedy, and performed as Henry Higgins in My Fair Lady.

In 1982, he graduated cum laude with a BFA in drama from the University of Washington (UW) as a student of the Professional Actor Training Program.

[20] MacLachlan was performing in Molière's Tartuffe at a Seattle-area theater when a casting agent for Dune producer Dino De Laurentiis began searching for a young lead and received multiple recommendations for him.

After several screen tests, he hit it off with director David Lynch, aided by their common Pacific Northwest backgrounds, and succeeded in winning the part.

He moved to Los Angeles in 1985,[8][22] and auditioned for several films, including Top Gun, but failed to win any roles, eventually dropping his agent.

[8] Lynch cast MacLachlan in the starring role of Jeffrey Beaumont in Blue Velvet (1986), which was received more positively.

Lynch commented on those roles in a GQ story about MacLachlan: "Kyle plays innocents who are interested in the mysteries of life.

[26] Lynch, who was known to allow his collaborative partners a large degree of control over their roles when working with him, rewrote scenes in Blue Velvet and Twin Peaks at the request of MacLachlan, who felt they were not right for his characters.

[30] In the 1993 film version of Franz Kafka's The Trial, with a screenplay by Harold Pinter, MacLachlan played the lead role of the persecuted Josef K.[31] MacLachlan co-starred with Samuel L. Jackson as a rookie prison guard in John Frankenheimer's 1994 Emmy-winning HBO film Against the Wall about the Attica prison riots.

[35] From 2000 to 2002, MacLachlan had a recurring role in the American television series Sex and the City, portraying Dr. Trey MacDougal, the one-time husband of Charlotte York (Kristin Davis).

[10] In the video game Grand Theft Auto III released in 2001, he voiced the character of the sociopathic real-estate developer Donald Love.

That same year he also had a guest role in Law & Order: Special Victims Unit, in which he played a psychiatrist who shot and killed a sociopathic child who had murdered his son.

[47] In 2010, after four years of playing Orson Hodge, MacLachlan decided to quit Desperate Housewives as he found the commute from his home in New York City to the set in Los Angeles increasingly difficult since becoming a father in 2008.

[26] In 2018, MacLachlan starred as Isaac Izard, the main antagonist in the fantasy-horror family film The House with a Clock in its Walls.

[69] In 2022, MacLachlan co-starred with Jon Hamm in Confess, Fletch[70] and was also cast as Chief Justice Earl Warren in Miranda's Victim.

[74] In 2024, he was honored with the Canal+ Icon Award at Canneseries ahead of his role in Amazon's Fallout, the adaptation of the popular video game series.

[77] In September 2024, he was cast alongside Connie Britton and Kaia Gerber in Overcompensating, a college-set comedy series created by and starring Benito Skinner.

[78] In January 2025, the WGAW announced that MacLachlan would posthumously present the Laurel Award for Screenwriting Achievement to David Lynch,[79] who had passed away earlier that month.

[80] MacLachlan had previously honored his longtime friend and collaborator with tributes in The New York Times,[81] GQ[82] and on his personal Instagram account, where he wrote, "My world is that much fuller because I knew him and that much emptier now that he's gone.