The Malcolm X and Do The Right Thing director will be the first black film-maker to take on the prestigious role.
Lee has premiered seven films at the festival. "Cannes will always have a deep spot in my heart," he said in a video message.
This year's event is due to take place in July instead of its usual May slot.
"Book my flight now. My wife Tonya and I, we're coming," the director added.
But with Covid-19 cases still at high levels in France, there is a chance that the event could be called off again.
"Throughout the months of uncertainty we've just been through, Spike Lee has never stopped encouraging us," festival president Pierre Lescure said in a statement.
"We could not have hoped for a more powerful personality to chart our troubled times."
Lee first made an impact on the film industry at Cannes in 1986 with She's Gotta Have It, which won the youth award. He returned to the festival three years later with Do The Right Thing, his landmark film about one day of charged race relations in Brooklyn.
Other Lee films to have been screened at Cannes have included Summer of Sam and BlacKkKlansman, while he is also known for Malcolm X and his latest release, Da 5 Bloods, about a group of US Army veterans returning to Vietnam.
The official selection for this year's festival, along with the rest of the jury, are due to be named in early June.
Hong Kong auteur Wong Kar-wai is the only Asian to have been president of the Cannes jury, while French-Algerian actress Isabelle Adjani was the first of African descent to preside in 1997.