Botin (pictured), father of Santander UK chief executive Ana, was considered one of Spain’s most powerful businessmen.
The bank’s share price fell 1.7% following the announcement.
He oversaw the rapid growth of Santander from a Spanish regional bank to a global player through purchases of institutions in Latin America and Europe.
Santander Group acquired Abbey National in 2010 along with the Bradford & Bingley savings business and branch network. The newly born Santander UK was merged with Alliance & Leicester later that year.
Botin was the third generation of his family to lead Santander and a replacement will be decided at a board meeting today. Ana Botin is seen as the frontrunner to succeed her father.