His major subsequent film roles include Boogie Nights (1997), Air Force One (also 1997), Magnolia (1999), Mystery Men (1999), Jurassic Park III (2001), Bobby (2006), Thank You For Smoking (2005), and Kingdom of the Planet of the Apes (2024).

[3] A "wretched student" by his own admission, he transferred to Goddard College in rural Vermont, where he studied under playwright David Mamet, and graduated in 1972.

After graduating from Goddard, Macy originated roles in a number of plays by collaborator David Mamet, such as American Buffalo[9] and The Water Engine.

He was required to join AFTRA in order to do the commercial, and received his SAG card within a year, which for an elated Macy represented an important moment in his career.

He has appeared in numerous films that Mamet wrote or directed, such as House of Games (1987), Things Change (1988), Homicide (1991), Oleanna (1994) (reprising the role he originated in the play of the same name), Wag the Dog (1997), State and Main (2000) and Spartan (2004).

Macy's leading role in Fargo (1996) helped boost his career and recognizability, though at the expense of nearly confining him to a narrow typecast of a worried man down on his luck.

[12] Other Macy roles of the 1990s and 2000s included Benny & Joon (1993), The Client (1994), Above Suspicion (1995), Mr. Holland's Opus (1995), Ghosts of Mississippi (1996), Air Force One (1997), Boogie Nights (1997), A Civil Action (1998), Pleasantville (1998), Gus Van Sant's remake of Psycho (1998), Happy, Texas (1999), Mystery Men (1999), Magnolia (1999), Panic (2000), Jurassic Park III (2001), Focus (2001), Welcome to Collinwood (2002), Seabiscuit (2003), The Cooler (2003), Cellular (2004), Sahara (2005), Everyone's Hero (2006) and Bobby (2006).

In a November 2003 interview with USA Today, Macy stated that he wanted to star in a big-budget action film "for the money, for the security of a franchise like that.

In 2007, Macy starred in Wild Hogs, a film about middle-aged men reliving their youthful days by taking to the open road on their Harley-Davidson motorcycles from Cincinnati to the Pacific Coast.

[15] Dirty Girl, which starred Macy along with Juno Temple, Milla Jovovich, Mary Steenburgen and Tim McGraw, premiered September 12, 2010, at the Toronto International Film Festival.

Macy has received high critical acclaim for his performance,[16] eventually getting an Emmy nomination for Outstanding Lead Actor in a Comedy Series in 2014.

In the 2012 film The Sessions, Macy played a priest who helps a man with a severe disability find personal fulfillment through a sex surrogate.

[17] He made his directorial debut with the independent drama Rudderless, which stars Billy Crudup, Anton Yelchin, Felicity Huffman, Selena Gomez and Laurence Fishburne.