Taylor (21-0) was wobbled and her face bloodied in the fifth round, but she hung tough and found the range on her right hand with excellent counter punching.
Serrano (42-2-1), a seven-division champion who moved up two weight divisions for this fight, lost for the first time since 2012.
Taylor defended her four titles for the sixth time, having been the undisputed champion at 61kg since a victory at Madison Square Garden in 2019 on the undercard of Andy Ruiz's upset of Anthony Joshua in a heavyweight title match.
"This was absolutely the best night of my career," Taylor said, ranking it ahead of her 2012 victory in the Olympic gold-medal match.
"I was told to enjoy every minute of it and that's what I did," Serrano said.
Maybe they'll do it again. Both sides talked of a rematch, perhaps next time in Ireland.