[1] Swinton began her career by appearing in Derek Jarman's experimental films Caravaggio (1986), The Last of England (1988), War Requiem (1989), and The Garden (1990).

She next starred in Sally Potter's Orlando (1992) and was nominated for a Golden Globe Award for her performance in The Deep End (2001), followed by appearances in Vanilla Sky (2001), Adaptation (2002), and Young Adam (2003).

Swinton won the Academy Award for Best Supporting Actress for playing a general counsel in the legal thriller Michael Clayton (2007).

She has also acted in films such as Constantine (2005), Burn After Reading (2008), I Am Love (2009), We Need to Talk About Kevin (2011), Only Lovers Left Alive (2013), Snowpiercer (2014), Suspiria (2018), Memoria (2021), The Eternal Daughter (2022), and The Room Next Door (2024).

Swinton has also gained popular recognition for playing the White Witch in The Chronicles of Narnia series (2005–2010) and the Ancient One in the Marvel Cinematic Universe franchise.

She is also known for her roles in the Wes Anderson films Moonrise Kingdom (2012), The Grand Budapest Hotel (2014), Isle of Dogs (2018), The French Dispatch (2021), and Asteroid City (2023).

In 1987, Swinton starred along Bill Paterson in Peter Wollen's Friendship's Death, she played a female extraterrestrial robot on a peace mission to Earth.

The part allowed Swinton to explore matters of gender presentation onscreen, which reflected her lifelong interest in androgynous style.

"People talk about androgyny in all sorts of dull ways," said Swinton, noting that the recent rerelease of Orlando had her thinking again about its pliancy.

Recent years have seen Swinton move toward mainstream projects, including the leading role in the American film The Deep End (2001), in which she played the mother of a gay son she suspects of killing his boyfriend.

She appeared as a supporting character in the films The Beach (2000),[24] featuring Leonardo DiCaprio, Vanilla Sky (2001), and as the archangel Gabriel in Constantine.

She was cast in the role of Elizabeth Abbott in The Curious Case of Benjamin Button, alongside Cate Blanchett and Brad Pitt.

[38] Also in 2009, she and Mark Cousins embarked on a project where they mounted a 33.5-tonne portable cinema on a large truck, hauling it manually through the Scottish Highlands, creating a travelling independent film festival.

[39][40] She had a starring role as the eponymous character in Erick Zonca's Julia, which premiered at the 2008 Berlin International Film Festival and saw a U.S. release in May 2009.

[46] Also in 2012, Swinton appeared in Doug Aitken's SONG 1, an outdoor video installation created for the Hirshhorn Museum and Sculpture Garden in Washington, D.C.

[48] In February 2013, she played the part of David Bowie's wife in the promotional video for his song "The Stars (Are Out Tonight)", directed by Floria Sigismondi.

[49] In 2015, she starred in Luca Guadagnino's thriller A Bigger Splash, opposite Dakota Johnson, Matthias Schoenaerts and Ralph Fiennes.

Swinton starred in Julio Torres's surrealist A24 comedy Problemista and David Fincher's action thriller The Killer both released in 2023.

[71] On February 2025, while given a speech at the Berlin film festival, Swinton called out the “the astonishing savagery of spite, state-perpetrated and internationally enabled mass murder”, as a response to Trump's plan to take over Gaza.

[72][73] Swinton signed a 2009 petition in support of director Roman Polanski, who had been detained while traveling to a film festival because of sexual abuse charges filed against him in a 1977 incident.

The petition argued that his detention undermined the tradition of film festivals as a place for works to be shown "freely and safely" and that the arrest of filmmakers traveling to neutral countries could open the door "for actions of which no-one can know the effects".

"[77] In January 2022, Swinton revealed she is recovering from long COVID, with symptoms including having trouble getting out of bed, a bad cough, vertigo, and memory loss.

She also stated that she was considering quitting acting to "retrain as a palliative carer", informed both by the trauma of living through the AIDS epidemic in the UK (feeling a similarity between her experiences and those of the characters in Russell T Davies's 2021 TV drama miniseries It's a Sin) and "witnessing the loving support her parents received from professional carers at the end of their lives, and the impact it had on her.