She was labeled "Queen of the Indies" for her roles in a succession of independent films throughout the 1990s,[1] such as Dazed and Confused (1993), Party Girl, The Doom Generation, Kicking and Screaming (all 1995), The Daytrippers (1996), The House of Yes, Clockwatchers (both 1997), and Henry Fool (1998).

Her more mainstream credits include You've Got Mail (1998), Scream 3 (2000), Josie and the Pussycats (2001), The Sweetest Thing (2002), Blade: Trinity (2004), Superman Returns (2006), Café Society (2016), and Beau Is Afraid (2023).

She frequently works with Christopher Guest and has co-starred in several of his mockumentaries: Waiting for Guffman (1996), Best in Show (2000), A Mighty Wind (2003), For Your Consideration (2006), and Mascots (2016).

On television, Posey appeared in the recurring role of Alice White on BYUtv's Granite Flats (2015), co-starred as Dr. Smith on all three seasons of Netflix's Lost in Space (2018–2021), and won critical acclaim for playing Freda Black in the HBO Max miniseries The Staircase (2022).

[8] They later moved to Laurel, Mississippi, where her mother worked as a chef and culinary instructor for the Viking Range Corporation in Greenwood and her father operated a car dealership.

[10] Posey got her first break in television with the role of Tess Shelby on the daytime soap opera As the World Turns.

[13][14] In an interview in January 2012, Parker said that the unofficial title has sometimes been a hindrance: I'm trying to work in studio movies, but they won't hire me.

Critical reaction to Posey's performance in the latter film was highly positive and earned her an MTV Movie Award nomination.

[20] Later the same year, she played the title character in Fay Grim, the sequel to Henry Fool, and appeared in For Your Consideration.

In 2007, Posey was cast in the lead role in the television series The Return of Jezebel James.

"[31] Lindsay Bahr of Entertainment Weekly said "Posey used her arsenal of talent and the material written and directed by C.K.

Posey appeared in Ned Rifle, the third and final film in Hartley's Henry Fool trilogy, again reprising her role of Fay Grim.

[34] On November 6, 2013, Hartley launched a fundraising campaign through Kickstarter to produce the film, netting a total of $384,000.

[37] In July 2014, it was announced that Posey had signed on to co-star in Woody Allen's mystery drama Irrational Man.

[43] In late 2019, Posey starred in an audio fiction podcast called Hunted wherein she plays the part of a U.S. Deputy Marshal tracking four escaped convicts from a federal maximum-security correctional facility.

[44] Posey appeared on Broadway in 2000, playing in Elaine May's Taller Than a Dwarf, which was directed by Alan Arkin.

She later appeared off Broadway in David Rabe's Hurlyburly in 2005, and then originated the role of Pony Jones in Will Eno's The Realistic Joneses in 2012.

Centered on the idea that the reader is sitting next to Posey on an airplane, the book mixes personal anecdotes from her career, random observations, stories about her life, and homemade photo collages.

According to Elle magazine, the memoir is "a humour-packed, irreverent, eccentric book packed with personal stories, whimsical how-tos and recipes, as well as collages made by her.

And she's gathered some good ones for her memoir, which also perfectly encapsulates the delightful weirdo you assume she is just by watching her play different people on screen.