Born in Everett, Massachusetts, Pompeo moved to Miami and then New York City, where a casting director discovered her and signed her for an ad campaign for L'Oreal.

A turning point came in her career in 2002, when she was noticed for her role in Brad Silberling's romantic drama Moonlight Mile.

In addition to her acting career, she has directed two episodes of Grey's Anatomy and founded a production company, Calamity Jane.

[11][12] In 2002, Pompeo was selected by director Brad Silberling for a lead role in his film Moonlight Mile, playing Jake Gyllenhaal's character's sympathetic love interest.

While generally praising the cast, Jeff Vice of Deseret News noted Pompeo's "extremely appealing" performance.

[17] Pompeo landed her first major role in 2005 on the ABC medical drama series Grey's Anatomy, created by Shonda Rhimes.

She has played the title character and series' protagonist, Meredith Grey, a surgical intern at the fictional Seattle Grace Hospital since the show's pilot episode.

"[19] Pompeo signed a new contract for Grey's Anatomy in 2011 that increased her salary to US$200,000 per episode; she was subsequently named the eighth highest-paid TV actress in 2012, earning $9 million.

[22] Pompeo's contract with the company expired again at the end of the 12th season along with the other original cast members, and she signed a new one with an increased paycheck.

[35] The view was echoed by later critics, including Mary McNamara of the Los Angeles Times who suggested that Pompeo, "who has worked very hard and against all narrative odds to make Meredith Grey an interesting character at last" should have received a nomination at the 61st Primetime Emmy Awards.

[38] On October 27, 2011, Deadline Hollywood reported that Pompeo had launched her own production company called Calamity Jane which sold its first project to ABC, an untitled show about female agents on the Secretary of State's security detail.

[39] During a 2014 BuzzFeed event, she expressed a lack of interest in acting after Grey's Anatomy completes its run; she explained: "I definitely feel myself transitioning.

"[40][41] Since then, Pompeo has been involved in other projects as a producer and had also made her directorial debut with a Grey's Anatomy episode, from the thirteenth season.

[44] Pompeo appeared in the music video for Taylor Swift's 2015 single "Bad Blood",[45] and two years later, she voiced a stuffed animal cat in Doc McStuffins.

[46] In January 2018, she renewed her contract for Grey's Anatomy, agreeing for two more seasons; she became the highest-paid actress in a television drama series, earning more than $20 million a year with the new deal.

She was also listed as co-producer for the Grey's Anatomy spinoff titled Station 19 and received office space for Calamity Jane at Walt Disney Studios.

They began dating after six months of friendship and got married in 2007, with the New York City mayor Michael Bloomberg as the legal witness to the ceremony.

[61] In the video, the actresses note that Olivia Pope, Annalise Keating, and Meredith Grey are "brilliant" and "complex" women who fight for justice and give voice to the voiceless.

Rhimes, Davis, Pompeo, and Washington each take turns speaking as they praise the presidential candidate and conclude: "Our characters are on television; the real world has Hillary Clinton."