He was 87.
The founder of the Las Vegas Sands casino company, Adelson was known for his support of conservative causes and Israel.
He was a significant backer of US President Donald Trump and Israeli Prime Minister Benjamin Netanyahu.
His death was caused by complications related to his treatment for non-Hodgkin's lymphoma, the Las Vegas Sands company said in a statement.
In a statement, former US president George W Bush said he mourned the passing of a "friend".