Blunt dropped out of drama school to make her professional debut in a 2001 production of The Royal Family directed by Peter Hall, which won her the Evening Standard Theatre Award for best newcomer. In 2003, she made her screen debut in the British television drama Boudica, about the life of the ancient British warrior-queen who fought the Romans. She also won considerable praise for her performance as the 16th-century queen Catherine Howard in the two-part British television drama Henry VIII.

Blunt's breakout however, was as Tamsin in the dark British movie, My Summer of Love in 2004, which portrayed a story of deception and lesbian love in the English countryside. For her role, she shared an Evening Standard British Film Award for Most Promising Newcomer with co-star Nathalie Press.

In 2005 she co-starred with Bill Nighy and Miranda Richardson in the British TV drama Gideon's Daughter, an original screenplay written and directed by Stephen Poliakoff, in which she played the troubled only child of New Labour spin doctor Gideon Warner, played by veteran British character actor Bill Nighy.

More recently, she starred opposite Meryl Streep and Anne Hathaway in the box-office success, The Devil Wears Prada. Streep and Hathaway received most of the critical attention initially, but Blunt, who had to lose weight for the role, proved to be equally memorable with Entertainment Weekly naming her the Best Female Scene-Stealer in their end-of-summer special issue. She appeared at the 79th Academy Awards where she co-presented the award for best costume design with her The Devil Wears Prada co-star Anne Hathaway.

Blunt later co-starred with Susan Sarandon in the independent drama Irresistible. When Sarandon became attached to starring in another movie, The Girl In The Park she strongly suggested that director David Auburn should cast her. Blunt did audition for the part - she almost received the role - but lost out to Kate Bosworth.