The Scream actress will appear in at least two episodes of the medical drama as the sister of Derek Shepherd (Patrick Dempsey), TVLine reports.
On the ABC series, Shepherd has four sisters, but only two - Amelia (Caterina Scorsone) and Nancy (Embeth Davidtz) - have previously appeared on-screen.
Campbell's character will arrive in Seattle in the aftermath of a tragic plane crash, which left Derek with a serious hand injury that likely spells the end for his career as a surgeon.
Canadian actress Campbell is best known for her roles in TV series Party of Five and the Scream horror movie franchise. She previously acted alongside Patrick Dempsey in Scream 3, in which he played her love interest.
Last year, the 39-year-old star signed a development deal for future scripted dramas and original movies with cable channel Lifetime.
Grey's Anatomy airs on Thursdays at 9/8c on ABC. In the UK, the series airs on Sky Living.
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