Sara was born in Mazatlán, Sinaloa, Mexico to parents of Mexican and Irish-American descent. At 8 years old, her parents divorced and she went to live with her mother in Tierrasanta, San Diego, California. She had an interest in music, which caught her mother's attention and was sent to San Diego School of Creative and Performing Arts. When she was in high school, she started to act in stage productions produced by the school. She graduated from Juilliard School with a Bachelor's of Fine Arts (Dramatics).
In an interview in 2011, she revealed she has suffered from severe depression. At one point, she could barely get herself out of bed to film Grey's Anatomy.
On June 17, 2011, Ramirez and longtime partner, Ryan Debolt, a business analyst at TIMEC, got engaged in Paris, France. They were married on July 4, 2012 in a private beachside ceremony in New York.
She is also an activist for LGBT rights and came out as bisexual and queer during a speech at the #40ToNone Summit on October 8, 2016. She was awarded the Ally for Equality Award by the Human Rights Campaign Foundation in 2015.