In 1997, when Sarah Drew was still in high school, she voiced Stacy Rowe on the animated series Daria. She also voiced the same character in Daria Television films, Is It Fall Yet? And Is It College Yet?. Things did not stop at the voicing stage, for in 2001, Sarah made her professional stage debut as Juliet in Romeo and Juliet at the McCarter Theatre in Princetown, New Jersey.
Her Broadway debut was in 2003 with Vincent in Brixton. That later took her to London’s West End. Sarah made a debut in television with a guest role in the Wonderfalls and also in the film called Radio. She appeared as Katie Burrell, the daughter of a Japanese relocation camp sergeant, in the American Pastime in 2007.
From 2004-2006, Drew played the role of Hannah Rogers in Everwood. She had a guest role on Cold Case, Law &Order: special Victims Unit, Medium, Castle, Glee, Privileged, Supernatural, and Private Practice. She also starred in Hallmark Hall of Fame film Front of the Class (2008). Drew had a recurring role as Kitty Romano in the AMC drama series Mad Men. In 2014, she starred in the film Mom’s Night Out.
In 2009, Drew played the role, Dr. April Kepner, in the Grey’s Anatomy medical drama series. She was cast in late September, and fast appeared in the sixth season episode “invasion” as one of the residents from Mercy West Hospital after its merger with Seattle Grace. Drew was brought aboard Grey’s Anatomy after previous collaborations with series creator Shonda Rhimes; she was featured as a guest in two episodes of private practice in 2008 and was the central cast member in Rhimes’ 2009 television pilot Inside The Box, which ABC passed on. In 2010, she got promoted to a series regular for the seventh time.
In March 2018, it got announced that Drew, alongside Jessica Capshaw, would be exiting Grey’s Anatomy. Following this announcement, Drew was cast as Detective Cagney in CBS’s Cagney & Lacey reboot pilot. In May 2018, CBS passed on the pilot. In 2019, Drew again cast as the title character in CBS pilot, as Sarah Cooper in “The Republic of Sarah,” but the project ultimately passed on by the network.