The tree dates back to the Ashanti Kingdom, part of modern-day Ghana.
Local people says the tree grew in the spot where renowned priest Komfo Anokye spat a kola nut on the ground in the early 1700s.
Many local people believed the black and white seeds of the kola tree could cure ailments and curses.
Ghanaians expressed outrage as pictures of the felled tree, in the town of Feyiase, circulated online.
The tree was in the middle of a major road linking Ghana's commercial hub Kumasi to Lake Bosomtwe.
It was spared during the construction of the highway because of its popularity and was a tourist attraction for Ghanaians and foreigners alike.
It is not clear why it was cut down now.
The director of research at Manhyia Palace, seat of the Ashanti royal family, Osei-Bonsu Safo Kantanka, told the BBC the site of the tree was significant in the history of the Ashanti Kingdom.
The Battle of Feyiase saw the Ashanti people battling for their independence against the powerful kingdom of Denkyira.
Mr Kantanka said the location of the tree "was the same spot the people of Denkyira were defeated by the Asantes".
Komfo Anokye was a powerful fetish priest - a person believed to act as a mediator between the spirit and living.
Oral tradition says he buried a sword in the ground, which remains firmly in place and can never be removed, on the premises of a hospital in Kumasi that bears his name.
The presence of the tree was a constant reminder of his exploits.
The authorities in Ghana have launched a manhunt for the people who cut down a famous 300-year-old kola tree, which was believed to have healing powers.