Police in New York said co creater Steve Ditko was found last month in his Manhattan apartment and was pronounced dead at the scene.
The comic book legend created the characters alongside Stan Lee.
Spider-Man's costume, web-shooters and his red and blue design all reportedly came from Ditko.
But from the 1970s he rarely spoke to reporters and declined almost every interview request.
Fans, including presenter Jonathan Ross and author Neil Gaiman, have paid tribute to the artist.
Ross, who met Ditko while making a documentary, described Ditko as "the single greatest comic book artist and creator who ever lived".
Ross tweeted: "I am beyond sad. For me, the single greatest comic book artist and creator who ever lived, Steve Ditko, is gone. Thank you for your tireless brilliance and boundless imagination, Steve, you uncompromising genius."
Neil tweeted: "Steve Ditko was true to his own ideals. He saw things his own way, and he gave us ways of seeing that were unique. Often copied. Never equalled. I know I'm a different person because he was in the world."
Ditko rose to fame for his work with Marvel Comics in the early 1960s.
He left the company in 1966 after he was said to have fallen out with Lee and went on to create superhero The Creeper with DC Comics.
TMZ reports the chief medical examiner listed the cause of death as arteriosclerotic and hypertensive cardiovascular disease.
Tobey Maguire first played Spider-Man back in 2002 with Andrew Garfield taking over in 2012 and Tom Holland also playing the leading superhero role.
Benedict Cumberbatch starred in 2016’s Doctor Strange, a film inspired by Ditko’s original creation.
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