The Primetime Emmy Award for Outstanding Guest Actress in a Drama Series, presented annually by the Academy of Television Arts & Sciences (ATAS), recognizes exceptional performances by actresses in guest roles on primetime drama series. It was first awarded on May 19, 1975, at the 27th Primetime Emmy Awards, with Zohra Lampert and Cloris Leachman as its inaugural winners.

The category has undergone several transformations, initially honoring single leading and supporting appearances in drama and comedy. It was re-introduced in 1986 as "Outstanding Guest Performer in a Drama Series" for both genders, before splitting into separate male and female categories in 1989 to adopt its current title. A new rule, effective from the 77th Primetime Emmy Awards, now makes performers ineligible if they were previously nominated for a lead or supporting award for playing the same character in the same series.

Patricia Clarkson, Cherry Jones, Shirley Knight, Margo Martindale, Amanda Plummer, and Alfre Woodard hold the record for most wins with two awards each, while Cherry Jones and Cicely Tyson share the distinction of having received the most nominations, with five each. Notably, the series Law & Order: Special Victims Unit has produced the highest number of awardees from a single program, with five winners in this category.