Popplewell, eldest of three children, is the daughter of Andrew Popplewell, QC, a barrister, and Dr. Deborah Lomas, an immunologist. Her paternal grandfather, Sir Oliver Bury Popplewell, was a former High Court judge. Her two siblings, Freddie Popplewell and Lulu Popplewell, who appeared in Love Actually, are also actors. She attended North London Collegiate School and was senior student 2006-2007.

She has a fear of mice, which required a double to do part of her scene at the Stone Table in The Chronicles of Narnia: The Lion, the Witch, and the Wardrobe.

Along with the actor of Edmund Pevensie in the Narnia series, Skandar Keynes, Popplewell supports Arsenal FC. They live around the corner from each other.

Popplewell began acting at the age of six, taking classes at the Allsorts Drama School. She began acting professionally in the TV production Frenchman's Creek in 1998. She made her film debut in 1999 in the film Mansfield Park and has since appeared in supporting roles in films like The Little Vampire (2000) and Girl with a Pearl Earring (2003).

Her first major role was in the film The Chronicles of Narnia: The Lion, the Witch and the Wardrobe (2005) where she played Susan Pevensie. She reprised her role in the sequel, The Chronicles of Narnia: Prince Caspian, which opened in theatres May 16, 2008.

She is currently studying English at Magdalen College, Oxford and was awarded the Cuppers Prize in 2007, for Best Supporting Actress, in the student production Five Kinds of Silence. In December 2007, she acted as Lady Macbeth in a student production of Macbeth at the Old Fire Station Theatre. From the 28-31 May 2008, Popplewell will star as Wendla Bergman in the once banned play, Spring Awakening, at the Oxford Playhouse.