[1][5] The family lived in multiple locations, including Alabama, Georgia, Texas, Panama, Nebraska, Alaska, New York, and Virginia, and Moore attended nine different schools.

[30] Playing artist Marian Wyman was an experience she found difficult, as she was a "total unknown" surrounded by established actors, but this proved to be Moore's breakthrough role.

[36] Following this, Moore was given her first leading role, playing an unhappy suburban housewife who develops multiple chemical sensitivity in Todd Haynes' low-budget film Safe (1995).

[2] The romantic comedy, directed by Chris Columbus and co-starring Hugh Grant, was poorly reviewed, but a box office success; it remains one of her highest-grossing films.

Director Paul Thomas Anderson was not a well-known figure before its production, with only one feature credit to his name, but Moore agreed to the film after being impressed with his "exhilarating" script.

[54] After re-uniting with Robert Altman for the dark comedy Cookie's Fortune (1999), Moore starred in An Ideal Husband – Oliver Parker's adaptation of the Oscar Wilde play.

Jodie Foster had declined to reprise the role, and director Ridley Scott eventually cast Moore, over Angelina Jolie, Cate Blanchett, Gillian Anderson, and Helen Hunt.

[62][63] Moore starred in three more 2001 releases: with David Duchovny in the science fiction comedy Evolution, in her husband's dramatic film World Traveler, and with Kevin Spacey, Judi Dench, and Cate Blanchett in The Shipping News.

[78][79] In 2005, Moore worked with her husband for the third time in the comedy Trust the Man,[16] and starred in the true story of 1950s housewife Evelyn Ryan in The Prize Winner of Defiance, Ohio.

[85] Ben Brantley of The New York Times was unenthusiastic about the production, and described Moore as miscast: in his opinion, she failed to bring the "tough, assertive" quality that her role required.

[103] Moore next starred with Annette Bening in the independent film[104] The Kids Are All Right (2010), a comedy-drama about a lesbian couple whose teenage children locate their sperm donor.

The role of Jules Allgood was written for her by writer-director Lisa Cholodenko, who felt that Moore was the right age, adept at both drama and comedy, and confident with the film's sexual content.

Following her well-received performance in What Maisie Knew,[115] Moore began 2013 with a supporting role in Joseph Gordon-Levitt's comedy Don Jon, playing an older woman who helps the title character to appreciate his relationships.

By drawing on King's writing rather than the 1976 film,[121] Mick LaSalle of the San Francisco Chronicle wrote that she managed to "[suggest] a history – one never told, just hinted at – of serious damage in [Margaret's] past".

[126] Described by The Guardian as a "grotesque, gaudy, and ruthless" character, Moore based her role on "an amalgam of Hollywood casualties she ha[d] encountered", and drew upon her early experiences in the industry.

[130] Moore played the supporting role of President Alma Coin, the leader of a rebellion against The Capitol, in the third installment of the lucrative The Hunger Games film series, Mockingjay – Part 1.

[132] Critic David Thomson wrote that Moore was "extraordinary at revealing the gradual loss of memory and confidence", while according to Kenneth Turan, she was "especially good at the wordless elements of this transformation, allowing us to see through the changing contours of her face what it is like when your mind empties out".

[136] She also appeared opposite Elliot Page in Freeheld, a drama based on a true story about a detective and her same-sex partner,[137] and in the romantic comedy Maggie's Plan, with Greta Gerwig and Ethan Hawke.

[138] In Maggie's Plan, Moore played a pretentious Danish professor, a comedic role which critic Richard Lawson of Vanity Fair deemed as the film's "chief pleasure".

[141] The film received negative reviews, with critics saying it failed to effectively portray American racism, but Geoffrey Macnab of The Independent praised Moore for giving "a perfectly judged comic performance as a Barbara Stanwyck-like femme fatale".

[144][145] Moore's final release of the year was the sequel to the 2015 spy film Kingsman: The Secret Service, subtitled The Golden Circle, co-starring Colin Firth, Taron Egerton, Channing Tatum, and Halle Berry.

[149] Stephen Dalton of The Hollywood Reporter believed she had delivered "an utterly natural and quietly spellbinding star performance,"[150] and The New York Times named her one of "the 10 best actors of the year.

[171] The film received considerable critical acclaim,[172][173] and Jonathan Romney of Screen Daily commended Moore for combining both "neurotic fragility and over-bearing brittleness" in her performance.

[176] The Independent's Nick Hilton found Moore "more effective in Mary's dramatic moments than her farcical ones,"[177] while Lucy Mangan of The Guardian called her performance "brilliant – cold, clever and always scintillating.

[189] Moore decided to write the book when her young son began disliking aspects of his appearance; she was reminded of her own childhood, when she was teased for having freckles and called "Freckleface Strawberry" by other children.

[200] In February 2025, under the second Trump administration, an executive order required about 160 Defense Department-run schools[201] to conduct a compliance review of books regarding “gender ideology” and “racial indoctrination”.

[1][210] Oliver Burkeman of The Guardian writes that her characters are typically "struggling to maintain a purchase on normality in the face of some secret anguish or creeping awareness of failure".

"[8] Ben Brantley of The New York Times has praised Moore's ability to subtly reveal the inner-turmoil of her characters, writing that she is "peerless" in her "portraits of troubled womanhood".

"[31] While raising young children, Moore spoke about how it affected her career choices, saying she selected roles that were practical for her as a parent and did not require her to be away for extended periods of time.

[129] Her recognized roles came in As the World Turns, Boogie Nights, An Ideal Husband, The End of the Affair, Magnolia, Far From Heaven, The Hours, A Single Man, The Kids Are All Right, Game Change, Maps to the Stars, and Still Alice.