The accident occurred near the town of Tome, in Biobio province, at about 1:00 am (0400 GMT), said Luciano Parra, a spokesman for the Tome mayor’s office.
“The information that we have right now shows that, unfortunately, 15 people did not survive, and 19 others were injured,” Parra told 24 Hours, a television news channel.
“Seven of those injured are in critical condition at the regional hospital,” he added.
The bus was carrying soccer fans from a game that was played the night before in the town of Talcahuano to their home town of Rancagua.
Parra said rescue teams had rushed to the scene but the fall had transformed the bus into a mangled mass of metal, slowing down the rescue process.
Police officers and firefighters were forced to extract survivors one by one, using saws, pliers and other equipment.
The exact cause of the accident is being investigated.
Tome is located about 500 kilometers (310 miles) south of the capital Santiago.