Hathaway began appearing in more dramatic roles after The Princess Diaries 2. She said that "anybody who was a role model for children needs a reprieve," although she also noted that "it's lovely to think that my audience is growing up with me", a reference to her previous status as a children's actress. She voiced Little Red Riding Hood in Hoodwinked! (2005), which received generally positive reviews. That same year, Hathaway starred in the R-rated Havoc, in which she played a spoiled socialite. In a surprise move, Hathaway was featured in several nude and sexual scenes throughout the film. Although the content of the movie was radically different from her previous films, Hathaway denied that her role in the film was a blatant attempt to be seen as more of a mature actress, citing her belief that doing nudity in certain movies is merely a part of what her chosen form of art demands of her; and because of that belief she does not consider appearing nude in the appropriate films to be morally objectionable.

After Havoc, Hathaway appeared opposite Heath Ledger and Jake Gyllenhaal in the drama Brokeback Mountain, in a role that further displayed a more serious side of her. Havoc was not released in theaters in the United States (but was later released in other countries) because of its weak critical reception, but Brokeback Mountain won rave reviews for its depiction of a homosexual relationship in the 1960s and received several Academy Award nominations. Hathaway would later assert that the content of Brokeback Mountain was more important than its award count and that making the film made her more aware of the kind of stories she wanted to tell as an actress.

Hathaway's next film was the 2006 comedy The Devil Wears Prada, in which she starred as an assistant to a powerful fashion magazine editor portrayed by Meryl Streep, whom Hathaway described as being "just divine." Hathaway said that working on the film made her respect the fashion industry a great deal more than she had previously, though she also claimed that her personal style is something she "still can't get right." In an interview with Us Weekly, Hathaway spoke about her weight loss for the film, stating, "I basically stuck with fruit, vegetables and fish [to slim down for the movie]. I wouldn’t recommend that. Emily Blunt and I would clutch at each other and cry because we were so hungry."

Hathaway was initially cast in the 2007 comedy Knocked Up, but dropped out before filming began and was replaced by Katherine Heigl. Writer/director Judd Apatow stated in a May 2007 issue of The New York Times Magazine that Hathaway dropped out "because she didn't want to allow us to use real footage of a woman giving birth to create the illusion that she is giving birth." In an August 2008 interview with Marie Claire magazine, Hathaway commented that she "didn't believe that it was necessary to the story." Hathaway was next seen in the 2007 drama Becoming Jane, in which she portrayed English writer Jane Austen. Also in 2007, Hathaway performed a selection from the musical Saturday Night for Stephen Sondheim's 75th Birthday and ASCAP Foundation Concert. Tim Burton considered Hathaway for the part of Johanna in his 2007 film Sweeney Todd: The Demon Barber of Fleet Street, but the role went to Jayne Wisener, a then-unknown actress, reportedly because Burton decided he wanted an unknown actress for the part.

• The Fiance (2010) (pre-production)
• Alice in Wonderland (2010) (post-production) .... The White Queen
  
• Bride Wars (2009) .... Emma
• Passengers (2008) .... Claire Summers
• Rachel Getting Married (2008) .... Kym
• Get Smart's Bruce and Lloyd Out of Control (2008) (uncredited) .... Agent 99
• Get Smart (2008) .... Agent 99
• Becoming Jane (2007) .... Jane Austen
• The Devil Wears Prada (2006) .... Andy Sachs
• Brokeback Mountain (2005) .... Lureen Newsome
• Havoc (2005) .... Allison Lang
• Hoodwinked! (2005) (voice) .... Red
• The Princess Diaries 2: Royal Engagement (2004) .... Mia Thermopolis
• Ella Enchanted (2004) .... Ella
• Nicholas Nickleby (2002) .... Madeline Bray
• Neko no ongaeshi (2002) (voice: English version) .... Haru
  ... aka The Cat Returns (International: English title)
• The Other Side of Heaven (2001) .... Jean Sabin
• The Princess Diaries (2001) .... Mia Thermopolis
• "Get Real" .... Meghan Green (13 episodes, 1999-2000)
       - Waiting (2000) TV episode .... Meghan Green
       - Tough Love (2000) TV episode .... Meghan Green
       - Falling from Grace (2000) TV episode .... Meghan Green
       - Choices (2000) TV episode .... Meghan Green
       - Denial (1999) TV episode .... Meghan Green
        (8 more)