The Comisión Nacional del Mercado de Valores (CNMV) announced on Tuesday Botín died of a heart attack.
Born in 1934 in the northern Spanish city of Santander, Botín came from a long line of bankers. His father and his uncle were both Chairmen of Santander Bank.
He began working for Santander in 1958 and within six years he was named director general.
Botín then became president in 1986, leading the bank to a series of mergers.
On his watch the Santander Group grew to become Eurozone's largest bank, and one of the largest in the world.
In 2013 it was ranked number 43 on the Forbes 2000 list of the world's biggest companies.
Botín's net worth was also estimated by Forbes to be €1.3bn ($1.7 billion) in 2005.
His public image was stained in 2010 when Spanish authorities discovered Swiss bank accounts, held by his family since the 1930s, and he was forced to make a €200 million settlement in order to make the High Court drop a tax evasion probe.
Botín is survived by his wife, Paloma O'Shea Artiñano, and six children.
Santander plans to hold a board meeting on Wednesday to nominate a new president, it said in a statement.
Botín's eldest daughter, Ana Patricia Botín, was named Santander Group President a few hours after his death.
Santander shares have fallen 2 percent to 7.6 euros since the news broke at 8.45 am.
More to follow