Wallace, who also played receptionist Carol Kester on "The Bob Newhart Show," was surrounded by friends and family when she died Friday night of complications from pneumonia, her son Michael Hawley, told the Los Angeles Times.
Wallace had surgery for breast cancer in March and was considered free of the disease, Hawley said.
"The Simpsons" Executive Producer Al Jean said the character of Springfield Elementary School teacher Mrs. Krabappel will be retired from the show, the Times reported.
"I don't intend to have anyone else play Mrs. Krabappel," Jean said. "I think Bart will get a new teacher."
Jean said the show's Nov. 3 episode will feature a tribute to Wallace.
"I was tremendously saddened to learn this morning of the passing of the brilliant and gracious Marcia Wallace," Jean said.
The series hinted earlier this year that a major character on "The Simpsons" would die this season, but Jean said it was not connected to Wallace's death, The Hollywood Reporter said.
"Earlier we had discussed a potential storyline in which a character passed away. This was not Marcia's Edna Krabappel. Marcia's passing is unrelated and again, a terrible loss for all who had the pleasure of knowing her," Jean said.
Wallace also appeared on "Bewitched," "The Brady Bunch," "Murder She Wrote" and "Full House."