Dozens more were injured in the accident near the town of Bambari, about 300km (186 miles) north-east of the capital Bangui.
Most of the victims are said to be traders heading to a nearby market.
Local residents often travel in overloaded lorries due to lack of other transportation in the country.
The cause of Wednesday's crash is now being investigated.
A local lawmaker said the lorry was travelling faster than normal.
"They were driving fast to make it to the market on time. That's what probably caused the accident," Amaseka Topi told Reuters news agency.
Dozens of injured people are being treated in Bambari's hospital. There are fears that the death toll could rise further.
Years of neglect have left much of the Central African Republic's road system in ruins, and safety regulations are rarely enforced.
The poor landlocked country has been wracked by conflict along religious and ethnic lines since 2013.
At least 77 people have been killed after a lorry loaded with passengers and goods crashed in the Central African Republic, officials say.