Trachtenberg was born in New York City to a Jewish family, the younger of two daughters of Lana, a bank manager, and Michael Trachtenberg, a fiber-optics engineer. Her father is from Germany and her mother was born in Russia, and Trachtenberg can speak Russian fluently. Her family celebrates both Christmas and Hanukkah; her grandparents live in Israel. Trachtenberg was raised, along with older sister Irene, in Sheepshead Bay in Brooklyn and attended P.S. 99 Elementary School and The Bay Academy for the Arts And Sciences Junior High School.

Trachtenberg made her first television appearance at the age of three, in a commercial for Wisk Detergent. She went on to feature in over 100 more commercials. She appeared in her first credited role as Nona F. Mecklenberg in The Adventures of Pete & Pete from 1994 until 1996. During the same period she played Lily Montgomery in All My Children, in which she first worked with future Buffy star Sarah Michelle Gellar.

Trachtenberg's film career began in 1996 with the lead role in Harriet the Spy. She then returned to television for Meego, for which she won a Young Artist Award. She returned to film in 1999 for Inspector Gadget, as the gadget-master's niece, Penny. She also starred in the film Can't Be Heaven. In the summer of 2000, Trachtenberg took up the role of Dawn Summers in Buffy the Vampire Slayer. She remained in the role until the show ended in 2003. After Buffy, she returned to film in the comedy movie EuroTrip, co-starring Scott Mechlowicz, Jacob Pitts and Travis Wester and directed by Jeff Schaffer. She also had a recurring role in the HBO series Six Feet Under as Celeste, a spoiled pop star for whom Keith Charles served as a bodyguard.

In March 2005, Trachtenberg played the title character in Walt Disney Pictures' family comedy/drama Ice Princess with Kim Cattrall. In this film, Trachtenberg plays a science whiz named Casey Carlyle who gives up her future academic life in order to chase her newfound dream of being a professional figure skater.

In November 2006, Trachtenberg guest starred in the sixth season of the Emmy-nominated crime drama Law & Order: Criminal Intent. In the episode "Weeping Willow", she played the role of Willow, a kidnapped video blogger based on lonelygirl15. Trachtenberg also made a cameo in the Fall Out Boy music video for "This Ain't a Scene, It's an Arms Race" (with "Buffy the Vampire Slayer" costar Seth Green), Joaquin Phoenix-directed video "Tired of Being Sorry" for Balthazar Getty's band Ringside, and Trapt's video "Echo". She was recently cast as the female lead in an ABC comedy pilot called The Hill, set in Washington, D.C. Trachtenberg provided the voice of Tika Waylan for Dragonlance: Dragons of Autumn Twilight, a direct-to-video animated movie based on the novel of the same name.

Trachtenberg appeared on the CW hit show Gossip Girl as Georgina Sparks, who recently left rehab and brings back the dark past Serena van der Woodsen desperately wants to leave behind.

She also guest stared in the the episode of House, M.D., "Safe". She revealed on the December 22, 2006, episode of Late Night With Conan O'Brien that House is her favorite show, she is friends with one of the producers and she asked to be a guest star. Trachtenberg also said she has a crush on Hugh Laurie, and during the scene in the elevator in which House searches her genital area for a tick, Trachtenberg said she played a joke on Laurie by putting a note between her legs that read "I Love You."

She will appear in the 2009 movie 17 Again, alongside Zac Efron.

• Melissa 1995 Lena (uncredited)
• Harriet the Spy 1996 Harriet M. Welsch
• Richie Rich's Christmas Wish 1998 Gloria
• Inspector Gadget 1999 Penny
• A Father's Choice 2000 Kelly McClain
• Can't Be Heaven 2000 Julie
• EuroTrip 2004 Jenny
• Mysterious Skin 2004 Wendy
• Ice Princess 2005 Casey Carlyle
• The Dive from Clausen's Pier 2005 Carrie Beal
• Beautiful Ohio 2006 Sandra
• Black Christmas 2006 Melissa
• The Hill 2007 Maggie Rogers
• Dragonlance: Dragons of Autumn Twilight 2008 Tika
• The Circuit 2008 Kylie Shines
• Kids in America 2008 Kitchelle Storms
• Against the Current 2008 Suzanne
• 17 Again 2009 Maggie O'Donnell