Anna Watson first debuted in The Amazing Spider-Man #15 and was created by Stan Lee and Steve Ditko.
Anna Watson is a paternal aunt to Mary Jane Watson. For some time, Anna tried setting her niece Mary Jane up with her good friend and neighbor May Parker's nephew Peter, but something always seemed to get in the way of their meeting. Eventually, the two aunts' efforts paid off, and Mary Jane and Peter became romantic interests for a great many years, with the two eventually marrying until history was altered by the demon Mephisto who supplanted it with the history of Earth-81545. At one point, May moved in with Anna so they could help and look after each other with their growing age when Peter moved out to go to college at ESU.
Following her friend May's supposed death, she moved in with Peter and Mary Jane. She found it odd that Peter would stay out for odd hours as well as his strange comings and goings. She thought he was having an affair, but this was later disproved to her all while keeping Peter's secret identity safe.
When Peter and Mary Jane had temporarily moved away to Portland, Oregon, Anna came across the clone Ben Reilly and mistook him for Peter. After a clever cover story for why he was there and why Mary Jane was not with him, Ben came to the conclusion that there could not be someone looking like Peter Parker in New York running around, as it would raise too many questions. Ben then dyed his hair blonde to further distinguish himself.
Upon May's eventual return, which had all been orchestrated by Norman Osborn (Including the "death"), Anna moved to Florida, all the while keeping in touch with May. She returned when May had been shot by a sniper's bullet and was present at May's wedding to J.Jonah Jameson, Sr.
In Other Media
Anna Watson appeared in Spider-Man:The Animated Series where she is best friends with May Parker, and portrayed a deep love of her niece. Throughout the show, she voiced her disapproval of Mary-Jane's relationship with the unreliable Peter Parker.
Anna Watson also appeared during the Spectacular Spider-Man.