Hamilton was born in New York City. She attended the Princeton University and later the Tisch School of the Arts in New York University. She starred in the number of theatre productions, including role of the title character in the original stage production of Cornelia, written by Mark V. Olsen. She made her television debut in the episode of NBC legal drama Law & Order in 1997, and as of 2003 began playing regular guest-starring roles, in shows like Star Trek: Enterprise, Nip/Tuck, Ghost Whisperer, Criminal Minds, The Closer, Castle, NCIS, Modern Family and True Blood.
Her memorable 2003 Star Trek Enterprise role of Feezal, the alien scientist and second wife of Doctor Phlox, explored the concept of Polygamy.
Hamilton played a supporting role in the 2004 film Promised Land, and the leading role in the 2006 film Sleeping Dogs Lie. She also appeared in the films Corporate Affairs (2008), Not Forgotten (2009) and God Bless America (2011).
On television, she had a recurring roles in the ABC comedy-drama series Desperate Housewives as Sister Mary Bernard, a nun trying to pursue married man Carlos Solis, and well on the AMC period drama Mad Men where she played the role of Anna Draper, polio survivor and widow of the "real" Don Draper. She also guest-starred on Grey's Anatomy and its spin-off Private Practice, and all of CSI shows: CSI: Crime Scene Investigation CSI: NY, and CSI: Miami. She also appeared in HBO drama series Big Love from 2009 to 2010.
In 2013, Hamilton was cast as Odessa Burakov in the Lifetime comedy-drama series Devious Maids. She worked with a dialogue coach to hone a Russian accent for her role in show. She appeared in the first two seasons. In 2015, she had the recurring roles in the USA Network series, Dig, and SundanceTV drama, Rectify.
