Season ten featured 14 actors appearing in a starring billing. All season thirteen cast members returned for the tenth year with the exception of Jerrika Hinton, who departed the series in the finale of Season 13.
- Ellen Pompeo as Meredith Grey
- Justin Chambers as Alex Karev
- Chandra Wilson as Miranda Bailey
- James Pickens Jr. as Richard Webber
- Kevin McKidd as Owen Hunt
- Jessica Capshaw as Arizona Robbins
- Sarah Drew as April Kepner
- Jesse Williams as Jackson Avery
- Caterina Scorsone as Amelia Shepherd
- Camilla Luddington as Jo Wilson
- Kelly McCreary as Maggie Pierce
- Jason George as Ben Warren
- Martin Henderson as Nathan Riggs
- Giacomo Gianniotti as Andrew DeLuca
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