Harris was born Estelle Nussbaum in Manhattan, New York on April 4, 1928, the younger of two daughters of Isaac (“Ira”) and Anna Nussbaum, Polish Jewish immigrants who owned a candy store. She moved to Tarentum, Pennsylvania, when she was seven years old to live near her aunt and uncle, who asked her father to work in their candy store. She graduated from Tarentum High School.

Since 1953, Harris has been married to window treatment salesman Sy Harris. They have two sons and one daughter.

In 1977, Harris began her career in Looking Up. She later became widely known for her supporting role as Estelle Costanza on Seinfeld. In Star Trek: Voyager, she portrayed the Old Woman who was actually a projection of the Nechani Spirits, in the unusually spiritual third-season Voyager episode “Sacred Ground,” which aired on October 20, 1996. She played a small role as Bridget in Out to Sea (1997). In Toy Story 2 (1999), she provided the voice of Mrs. Potato Head and would continue to reprise the role for the franchise. In 2005, she lent her voice to Mama Gunda in Tarzan II. In The Suite Life of Zack & Cody, Harris had a recurring role as Muriel. In 2007, she appeared in Brad Paisley’s music video for the song “Online.” Harris reprised her role of Mrs. Potato Head in Toy Story 3 (2010). She portrayed Bertha Kristal, the mother of CBGB founder Hilly Kristal, in CBGB (2013).