Botín, age 54, ranked number 18 on the Forbes list of the 100 most powerful women on Tuesday, above such icons as Beyoncé Knowles (21st place), American politician Nancy Pelosi (38) and British Queen Elizabeth II (41).
At the very top of the list was German Chancellor Angela Merkel, taking first place for the fifth time in a row, followed by Hillary Clinton in second place.
Botín currently serves as executive chair of Spanish banking giant Santander Group, the largest bank in the eurozone by market value and one of the largest banks in the world.
"Ana Patricia Botín became one of the most powerful banking executives in the world and the first woman to head a major European lender in September 2014 when she stepped up to the position of executive chairman of financial-services behemoth Santander Group of Spain," Forbes wrote.
Botín took the reins at Santander Group after the death of her father, Emilio Botín, who died in 2014 of a heart attack.
Before that, she served as CEO of Santander UK and was appointed as a director of the Coca-Cola Company by the firm's board.
Botín also is a mother of three.
The Cantabrian-born heir to a banking family that has led Santander for four generations, Botín has been named a powerful figure several times before, first making it onto the Forbes list a decade ago at number 99.
She was also named the top European businesswoman by Financial Times in 2005 and 2006.
Other women appearing on this year's Forbes list included politicians, technology leaders, finance experts, entertainers, philanthropists and billionaires.
The youngest was singer Taylor Swift, age 25, who came in at number 64.