Popplewell began acting at the age of six, taking classes at the Allsorts Drama School. She began acting professionally in the TV productionFrenchman'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, in which she acted with William Moseley, Skandar Keynes, Georgie Henley and Ben Barnes. The movie opened in theatres 16 May 2008. She hasphobia 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.