DeFer was born in Tucson, Arizona. In 2003, she moved to Los Angeles to pursue a career in acting.
DeFer made her acting debut in a March 2004 episode of the Nickelodeon sitcom Drake & Josh. She has since made a number of guest appearances on television shows such as Quintuplets, Ghost Whisperer, CSI: Miami, and How I Met Your Mother. DeFer appears on the cover of Reeve Oliver's second album, Touchtone Inferno (2007).
In May 2004, DeFer was cast as Scarlett on The WB's drama series The Mountain. The series follows the personal lives of the staff and friends at a remote ski resort. The series premiered on September 22, 2004, but was cancelled after four months.
In April 2005, DeFer landed a role on the Fox sitcom The War at Home. The series centers on the day-to-day life of Gold family whom reside in Long Island, New York. DeFer portrayed teenager Hillary Gold, the eldest child who frequently misbehaves. The series premiered on September 11, 2005 to 7.2 million viewers, but received generally negative reviews from critics. The series ran for two seasons.
DeFer starred in her theatrical film debut Flicka, released in October 2006. DeFer portrayed the film's antagonist, Miranda Koop. In 2011, DeFer starred in the low-budget Western film Mattie, which was released on DVD under the title Renegade.
In April 2011, The CW announced DeFer would have a major-recurring arc in both the fourth and fifth seasons of Gossip Girl. DeFer had previously auditioned for the role of Raina Thorpe, but she did not receive the part. DeFer portrayed the role of Ivy Dickens, a con artist who pretends to be Charlotte "Charlie" Rhodes in order to get access to the latter's trust fund. DeFer was reunited with The Mountain castmate Penn Badgley. The critical reception of the character had been positive until her appearance in the fifth season received less than favorable reviews. DeFer reprised her role of Ivy in the series' sixth and final season and was listed as a main cast member.
In January 2012, DeFer called off her engagement to jewelry designer Mike Pereria, whom she had been dating on and off since 2002.
DeFer subsequently began dating Michael Fitzpatrick, lead vocalist for the band Fitz and the Tantrums, and in May 2013, she announced that they were expecting a child together. They welcomed their son, Theodore Ignatius, on September 20, 2013. The couple got married on July 25, 2015. They welcomed their second son, Sebastian Danger, on April 11, 2017.
|The Powder Puff Principle||Young school board president||2006||Short film|
|In My Pocket||Molly||2011|
|Drake & Josh||Girl that complains too much||2004||Episode: "Guitar"|
|North Shore||Emily||2004||Episode: "Secret Service"|
|The Mountain||Scarlett||2004-05||Recurring role; 6 episodes|
|Listen Up!||Brooke||2005||Episode: "Inky Dinky Don't"|
|The War at Home||Hillary Gold||2005-07||Main role; 44 episodes|
|Shark||Katie Dobbs||2007||Episode: "Shaun of the Dead"|
|Family Guy||Dakota||2008||Voice; Episode: "Tales of a Third Grade Nothing"|
|Ghost Whisperer||Angie Halsenback||2009||Episode: "This Joint's Haunted"|
|Bones||Tory Payne||2009||Episode: "The Gamer in the Grease"|
|CSI: Miami||Valerie Metcalf||2010||Episode: "Getting Axed"|
|How I Met Your Mother||Casey||2010, 2013||2 episodes|
|Gossip Girl||Ivy Dickens / Charlotte "Charlie" Rhodes||2011-12||Guest role (Season 4); main role (Seasons 5-6); 39 episodes|
|Friends With Benefits||Mary Webber||2011||Episode: "The Benefit of Mentors"|
|Layover||Rebecca White||2012||Television film|