Santana won four major singles championships - at the French Open in 1961 and 1964, at the US Open in 1965 and at Wimbledon in 1966, the same year he reached the world No.1 ranking.
"It's difficult for a genius to be rewarded in tennis and Manolo was one of those few who could," Gene Scott said at Santana's induction ceremony when the Spaniard entered the International Tennis Hall of Fame in 1984.
"He literally invented one of the strokes that we now see in profusion - the backhand topspin lob."
Rafael Nadal joined in the flood of condolences on social media, writing in Spanish that "we will all miss you Manolo."
"You will always be one of a kind and special," Nadal wrote.
"As I have said many times in the past: a thousand thanks for what you did for our country and for opening the way for others. You were always my role model, a friend and someone who was close to all of us."
Garbine Muguruza posted a photo of her with an elderly Santana with the message thanking him for his "goodness, warmth, and for showing us the way forward."
The two-time grand slam winner added: "You were always our reference point, for everyone in Spanish tennis, a pioneer.
"So close and so attentive, in the good and bad times. We will miss you. All my love for your family and loved ones."
Spain's king and prime minister echoed the sentiments of Nadal, calling Santana a "legend."
"There are people who become legends and make a country great. Manolo Santana was and will always be one of them," King Felipe VI wrote on Twitter.
Spanish Prime Minister Pedro Sanchez said: "He won Roland Garros, the US Open and Wimbledon, a total of 72 tournaments and an Olympic gold to make him a tennis legend and one of the best athletes our country has seen."
Billie Jean King fondly recalled winning her first Wimbledon title alongside Santana's triumph there in 1966.
"We danced the 1st dance at the Ball," King wrote on Twitter.
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