In 1998, Murphy was named VH1/Vogue's "Model of the Year". She played "Dubbie" in Barry Levinson's film Liberty Heights. She was one of the "Modern Muses" on the November 1999 Millennium cover of American Vogue and was chosen to represent Calvin Klein's perfume "Contradiction". In 1998, during a photo shoot for Elle magazine, the photographer noticed her resemblance to the actress Gene Tierney and dubbed her "The blonde Gene Tierney".
Murphy has shot campaigns for Missoni, Versace and Tiffany & Co. In 2005 she was featured on the cover of the Sports Illustrated Swimsuit Issue.