Annable was born in Los Angeles, California. Her mother, Lydia (née Nodarse), is Cuban. Her father, Victor Yustman, who is of Italian and French descent, was born in Bogotá, Colombia, and raised in Nicaragua. After her graduation from Woodcrest Christian High School in Riverside, California, she had planned to earn a degree in business finance at Loyola Marymount University, and only then resume her career in acting full time, but she dropped that idea as irrelevant to her true passion for acting.
Annable made her acting debut at an early age, playing a young, Spanish-speaking student named Rosa in Kindergarten Cop, and later moved on to various television shows and movies such as South Beach and October Road. In 2007, she starred in the Lifetime original movie Reckless Behavior: Caught on Tape and followed it quickly with a lead role in J. J. Abrams' Cloverfield. In addition to this, she made a short appearance in the John C. Reilly comedy film Walk Hard. She also provided the voice of the character Amata in Fallout 3. On January 29, 2008, Variety announced that she would appear in The Unborn, which was released in 2009.
She is featured in the 2009 music video for "(If You're Wondering If I Want You To) I Want You To" by Weezer.
She starred as Melanie in the Fox comedy, Breaking In. August 24, 2011, the show was renewed by Fox for thirteen episodes and was scheduled to air in the midseason comedy block. Fox canceled the series May 2011 and it ended its run April 2012.
In October 2011, Annable began starring in Fox's House as Dr. Jessica Adams, a former prison doctor hired by Dr. Gregory House to join his team. She made her first appearance in the eighth season premiere titled "Twenty Vicodin" and remained on the show until it ended with the 22nd episode titled "Everybody Dies" in May 2012.
In February 2013, Annable signed on for the lead role of the ABC drama pilot Westside produced by McG and developed by Ilene Chaiken, but it was not picked up as a series.
In March 2014, Annable was cast as Trudy Cooper in the ABC series The Astronaut Wives Club.