Lively started out in film with a bit role in Sandman in 1998. In 2005, Lively played Bridget in The Sisterhood of the Traveling Pants, for which she received a Teen Choice Award nomination for "Choice Movie Breakout - Female." She reprised the role in 2008 in the sequel, The Sisterhood of the Traveling Pants 2. She starred in Accepted, Simon Says, and Elvis and Anabelle in 2006. She received the Breakthrough Award from Hollywood Life for her role in Accepted in December 2006.

Lively was cast in the CW's series Gossip Girl which premiered in September 2007. She plays Serena van der Woodsen in the teen drama. While rumors of infighting among the Gossip Girl co-stars have circulated in the tabloids, Lively denies that there is any unfriendly competition on-set. “The media is always trying to pit us against each other," she said in an interview, "I guess because it’s just not interesting to say, ‘Everyone gets along; everybody just works 18-hour days and goes home to sleep.’ That’s not fun to read, I guess.” Her first magazine cover was the November 2007 issue of Cosmo Girl, where she discussed her time in high school and her career prior to Gossip Girl.

She has since appeared on the January 2008 cover of shopping magazine Lucky. She has more recently appeared on the March 2008 cover of Teen Vogue, as well as the May 2008 cover of NYLON with her Gossip Girl co-star Leighton Meester. She appeared on the cover of "Seventeen"'s August 2008 issue. The star also was on the cover of "Girls' Life"'s August 2008 issue, along with The Sisterhood of the Traveling Pants costars Amber Tamblyn, Alexis Bledel, and America Ferrera. More recently Lively also appeared on the cover of "Cosmopolitan"'s September 2008 issue. Lively has a brief cameo in a pre-recorded Saturday Night Live skit entitled "Murray Hill" alongside James Franco, where she portrays a transexual partygoer.

• The Private Lives of Pippa Lee (2009) (completed) .... Teenage Pippa Lee
  
• "Gossip Girl" .... Serena van der Woodsen (35 episodes, 2007-2008)
       - Gone with the Will (2008) TV episode .... Serena van der Woodsen
       - Episode #2.14 (2008) TV episode .... Serena van der Woodsen
       - O Brother, Where Bart Thou? (2008) TV episode .... Serena van der Woodsen
       - O Brother, Where Bart Thou? (2008) TV episode .... Serena van der Woodsen
       - It's a Wonderful Lie (2008) TV episode .... Serena van der Woodsen
        (30 more)
• "Saturday Night Live" .... Transvestite (1 episode, 2008)
  ... aka NBC's Saturday Night (USA: first season title)
  ... aka SNL (USA: informal title)
  ... aka SNL 25 (USA: alternative title)
  ... aka Saturday Night (USA: second season title)
  ... aka Saturday Night Live '80 (USA: sixth season title)
  ... aka The Best of Saturday Night Live (USA: rerun title)
       - James Franco/Kings of Leon (2008) TV episode (uncredited) .... Transvestite
• New York, I Love You (2008) .... Girlfriend
  ... aka New York, je t'aime (France: literal title)
• The Sisterhood of the Traveling Pants 2 (2008) .... Bridget Vreeland
• Elvis and Anabelle (2007) .... Anabelle
• Simon Says (2006) .... Jenny
• Accepted (2006) .... Monica
• The Sisterhood of the Traveling Pants (2005) .... Bridget
  ... aka The Sisterhood of the Travelling Pants (Australia)
  
• Sandman (1998) .... Trixie / Tooth Fairy