The pair join Alan Shearer and Thierry Henry who became the first two inductees last month.
Cantona spent five seasons with Manchester United, winning four Premier League titles and providing countless moments of inspirational moments while Keane won seven Premier League titles in a 12-year spell at Old Trafford.
“I am very happy and very proud, but at the same time I am not surprised,” Cantona told the Premier League’s official website.
"I would've been surprised not to be elected!
"I have been lucky to play in this team, with wonderful players, a wonderful manager and wonderful fans."
"We have nearly 30 players who could have been elected. Me, it's different. If you have to elect one, it's me. The other ones are all great... Me, I am exceptional!"
Keane added: "I feel very lucky to be inducted but I’ve only been inducted because of the players I’ve played with."
Four more players from a shortlist of 21 will be added to the 2021 Hall of Fame list.
Only players who have retired from professional football will be selected and their selection will be based solely on their performance in the Premier League.
The criteria for selection means the likes of Cristiano Ronaldo, Sergio Aguero and David Silva, who are all still playing professionally, will not be considered for induction just yet.