She is the wife of George Bush, she was seen living in the White House, and later moved across the road from the Simpsons with her husband.
She is shocked that when the Simpsons are touring the White House they feel entitled to go into the private quarters of the presidential family and that they see her in the bathtub. Despite being rightfully annoyed at first, Mrs. Bush softens her tone when she sees the Simpson family is wearing VIP badges. Later, Barbara Bush is much more courteous, making friends with Marge. Both Marge and Mrs. Bush are annoyed by the fact their husbands bicker and eventually fight, agreeing that both men act in a pig-headed manner. After Bush apologizes to Homer for spanking his son, Bart, she bids farewell to Marge as she and her husband sell the house and leave Springfield for good before the house is bought by another former U.S. president, Gerald Ford who becomes friends with Homer.
She is voiced by Maggie Roswell.
- Barbara is based on the real-life first lady and wife of George H. W. Bush who was the president of the United States from 1989 to 1993.
- Her relationship with Bart is a parody of Mrs. Wilson's relationship with Dennis from Dennis the Menace.