Following her role in the period drama series Downton Abbey (2012–2015), her film breakthrough was the title role in Cinderella (2015).
Her television credits include Ethel Brown in the 2010 BBC production of Richmal Crompton's Just William, Poppy in the fourth series of ITV's Secret Diary of a Call Girl (2011), and Lady Rose Aldrige in Downton Abbey. Lady Rose became a main character in the fourth and fifth series of the programme. James also appeared as Lady Rose in the series finale.
In 2012, Lily James played the role of Katrina in Play House and Marijka in Definitely the Bahamas in a double-bill written and directed by Martin Crimp at the Orange Tree Theatre in Richmond, London as part of the theatre's 40th anniversary.
James played Cinderella in Kenneth Branagh's 2015 live-action Disney film Cinderella. Lily James was photographed by Annie Leibovitz as Cinderella, in the blue gown her character wears to the ball, for the December 2014 issue of Vogue. James also made her singing debut in the film singing "Sing Sweet Nightingale," "Lavender's Blue" and "A Dream Is a Wish Your Heart Makes" from the 1950 animated film in the end credits.
In 2016, she returned to television in the 2016 BBC historical drama series War & Peace, playing Natasha Rostova. She also starred in her second major film, as Elizabeth Bennet in the action-horror film Pride and Prejudice and Zombies, a parody of Jane Austen's Pride and Prejudice.
In 2017, she appeared in several major films. She played Debora, the love interest of the main character, Baby, in Edgar Wright's action film Baby Driver. She played Elizabeth Layton, a secretary to British Prime Minister Winston Churchill (played by Gary Oldman), in Joe Wright's war drama film Darkest Hour. She also headlined the World War II drama film The Exception, playing a British agent posing as a servant to the exiled Kaiser Wilhelm II.
In 2020, Lily James played the second Mrs de Winter in an adaptation of Daphne du Maurier's Gothic romance Rebecca directed by Ben Wheatley and co-starring Armie Hammer.