For her portrayal of Anne, Queen of Great Britain in the period black-comedy film The Favourite (2018), Colman won the Academy Award for Best Actress.

Her other notable film credits include Tyrannosaur (2011), The Iron Lady (2011), Hyde Park on Hudson (2012), Locke (2013), The Lobster (2015), Empire of Light (2022), Puss in Boots: The Last Wish (2022), Wonka (2023), Wicked Little Letters (2023), and Paddington in Peru (2024).

She has appeared in a number of BBC, ITV and Channel 4 television series, such as People Like Us, Look Around You, Black Books, The Office and The Time of Your Life.

She regularly appeared on BBC Radio 4 comedies, such as Concrete Cow, Think the Unthinkable, The House of Milton Jones and Dirk Gently's Holistic Detective Agency.

She decided to leave the programme after her agent suggested that she was becoming too closely associated with their work and needed to widen her horizons, a decision which was made "with tears".

Colman appeared the following year in the BBC drama Exile, written by Danny Brocklehurst and starring John Simm and Jim Broadbent.

From 2011 to 2012, she played Ian Fletcher's (Hugh Bonneville) lovelorn secretary Sally Owen in Twenty Twelve, a comedy series about planning for the 2012 Olympic Games in London.

The crime-drama series, set in the fictional Dorset town of Broadchurch, follows the residents of a tightly-knit community after a young boy is found dead on a beach under suspicious circumstances.

[25] Colman was praised for her performance as Angela Burr in the 2016 AMC-BBC miniseries The Night Manager, for which she was nominated for the Primetime Emmy Award for Outstanding Supporting Actress in a Limited or Anthology Series or Movie, in addition to winning the Golden Globe Award for Best Supporting Actress – Series, Miniseries or Television Film.

[28] She played Hildegarde Schmidt, Princess Dragomiroff's lady's maid, in Kenneth Branagh's 2017 remake of Agatha Christie's Murder on the Orient Express.

In 2018, Colman starred as Queen Anne in Lanthimos' satirical dark comedy The Favourite alongside Emma Stone and Rachel Weisz.

[38] Colman received positive reviews for her supporting role as Madame Thénardier in the 2018 BBC miniseries Les Misérables, an adaptation of the novel of the same name.

[42][43] The fourth season was released on 15 November 2020, to universal acclaim and earned her the Primetime Emmy Award for Outstanding Lead Actress in a Drama Series.

[44] Colman starred with Anthony Hopkins in Florian Zeller's 2020 film adaptation of his stage play, The Father, which focuses on an elderly man dealing with memory loss.

Colman was executive producer and starred with David Thewlis in the HBO true-crime miniseries Landscapers created by her husband, Ed Sinclair.

[50] Colman also starred that year in Maggie Gyllenhaal's psychological drama The Lost Daughter, an adaptation of the novel of the same name by Elena Ferrante.

[57][58] In 2023, Colman starred as Miss Havisham in the FX / BBC period drama series Great Expectations, based on Charles Dickens' novel of the same name.

[66] In May 2024 it was announced that Colman would be starring alongside John Lithgow in Jimpa, directed by Australian director Sophie Hyde and filmed in South Australia, Amsterdam, and Helsinki.

[72] Their professional collaborations include the 2021 miniseries Landscapers created and co-written by Sinclair, and the films Wicked Little Letters (2023) and The Roses (upcoming) which they produced together; Colman played the female lead in all of these works.

[73] In August 2014, she was one of 200 public figures who signed a letter to The Guardian opposing Scottish independence in the run-up to the September 2014 referendum on the issue.

[74] In an interview with The Sunday Times in November 2019 on her portrayal of Queen Elizabeth II in The Crown, Colman described herself as a "leftie monarchist", having previously been a life-long republican.

[76] In November 2023, Colman signed a letter that called for a ceasefire in the Israel–Hamas war and condemned western cultural institutions for "repressing, silencing and stigmatising Palestinian voices and perspectives.

Colman believes that "the media industry has huge influence and with that comes a responsibility to contest the stigma that sadly still exists, through accurate representation".

[8] Inspired by her research for the film Tyrannosaur, in 2014, Colman became the patron of the UK charity Tender, which uses theatre and the arts to educate young people about preventing violence and sexual abuse.

[80] She has also supported charity campaigns for the Marie Curie Great Daffodil Appeal for the terminally ill.[81] In December 2014, Colman was involved in a BBC Radio documentary about the plight of women in Afghanistan for Amnesty International UK.