"There is a high number of people who appear to have died", Cuban president Miguel Diaz-Canel said from the scene, adding that the survivors were seriously injured.
Meanwhile, Cuban authorities told a news conference on Saturday at Havana airport that 99 of the passengers killed on the domestic flight to the eastern city of Holguin were Cuban, while three were foreign tourists - two Argentines and a Mexican - and two were Sahrawi residents in Cuba.
The fire from the crash had been put out and authorities were identifying bodies, the president said.
The aircraft was nearly completely destroyed in the crash and fire that followed.
"It crashed between the locality of Boyeros and the village of Santiago de La Vegas", state-run TV said in its midday news broadcast, referring to an area about 20 kilometres south of Havana.
The last deadly accident involving a Cubana-operated plane was in 1989, when a charter flight from Havana to Milan, Italy, crashed shortly after takeoff, killing all 126 people on board and at least two dozen on the ground.
In 2010, a commercial Aero Caribbean plane crashed in central Cuba and all 68 people on board were killed. The Mexican government said Mexicans citizens were among the dead, without providing further details.
The lights in the airport suddenly went out, he said, and he was told a plane had crashed.
Eyewitness and private salon owner Rocio Martinez said she heard a odd noise and looked up to see the plane with a turbine on fire. "All of a sudden, it made a turn, and went down".
A US State Department official said the agency was not aware of any request for US assistance at this time, but the National Transportation Safety Board and Federal Aviation Administration had offered to assist in the investigation.
Yasniel Diaz, a 21-year-old musician, said the pilot appeared to attempt an emergency landing, but crashed instead.
"I started running, I was so afraid".
The Boeing and its Mexican crew had been leased to Cuba's state airline Cubana de Aviacion by a Mexican company, Global Air, also known as Aerolineas Damojh.
Smoke can be seen billowing from the debris that litters the ground while pictures from the scene appear to show victims being stretchered out of the site.
But there have been several serious air disasters this year.
"She is alive but very burnt and swollen", said a distressed relative of one of the survivors at the hospital.
One of the plane's black boxes has been retrieved, officials said.
Aviation authorities in Guyana past year stopped the same aircraft from conducting charter flights because of serious safety concerns, including fears about excessive baggage overloading and other issues.
- Once-missing teachers, students among ones killed in Santa Fe shooting
- George Clooney and Wife Expected to Attend Royal Wedding
- Tom Brady can't use old excuse for this Patriots blow-off
- Speaker Ryan Fails to Pass Farm Bill
- Santa Fe HS student Shana Fisher killed in mass shooting, mother says
- Happening today - a new plan will be unveiled regarding Iran
- Kentucky Derby Winner Justify Is Favored To Win Soggy Preakness
- Record score denies Leishman victory
- These are the victims of the Santa Fe High School shooting
- Tennis betting could increase a lot in U.S. , says FanDuel CEO