The former president, who was diagnosed with lung cancer in August 2019, is said to have died at 03:00 local time (06:00 GMT), according to local media.
His son, Alvaro wrote on Twitter that his father died home, surrounded by family and friends.
"On behalf of the family, we want to thank all Uruguayans for the love received by him over so many years", the post said.
Vazquez was born in 1940 and graduated from medical school. He won the Uruguayan presidential race with 52.8 percent of the vote in 2014 and served as the country's president from 1 March 2015 to 1 March 2020.
He previouly occupied the president's post from 2005 to 2010.
