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.

Heidi Gannon was born in Wales and her sister Jo Baines was born in England about two hours afterwards.
Their mum didn't know she was having twins.
A set of twins were born in England and Scotland in 2012 and were thought to be the first to be born in different countries but Heidi and Jo were born much earlier, in 1976.
The family has been in touch with Guinness World Records which has confirmed they will update their records.
A spokesperson said: "We were made aware of Ms Baines and Ms Gannon's claim for this record last week and after some research involving our twins consultant we have been able to verify that they are indeed the first twins born in different countries."

The ex-Middlesex captain moved to Lord's from Essex in 2009 and has scored 5,977 first-class runs since making his debut for Kent in 2005.
Dexter, 31, has taken 28 wickets in all formats this season and is two scalps short of his 100th first-class wicket.
"It's a bit of a coup for the club," elite performance director Andrew McDonald told BBC Radio Leicester.
"It is nice to have someone of Dexter's experience, leadership qualities and skill set join the club.
"What he will offer in all three formats of the game is going to be superb. We felt that the little bit of extra experience was needed for this group to be the real deal next season.
"It is a good sign when players like Dexter approach us. It shows the steps forward we are taking on and off the field."

The submarine, one of the Russian navy's most advanced vessels, sank in the Barents Sea on 12 August, 2000 with the loss of all 118 people on board.
An explosion of fuel from an old torpedo caused the disaster.
Moscow's response to one of the greatest disasters in Russian naval history was widely criticised.
Relatives and members of Russia's northern fleet are due to cast wreaths into the sea on Thursday in memory of the crew.
Flags are being flown at half-mast at the headquarters of all Russia's naval fleets, and a ceremony and minute's silence was being held at Moscow's Central Army Museum.
The initial response to the disaster in 2000 was shambolic, says the BBC's Richard Galpin.
After radio contact was lost there was a still unexplained delay before a search and rescue mission was launched.
Although the submarine was lying just 100m below the surface of the sea, attempts to locate it and reach it repeatedly failed.
It was days before the authorities informed relatives that something was wrong and the then President, Vladimir Putin, initially remained on holiday.
Russia eventually accepted international assistance, but when Norwegian divers opened the Kursk's hatch 10 days later they found the boat flooded and everyone dead.
Many had died within seconds of the initial explosion, but others survived for several hours, a report found.
Russian officials originally suggested the submarine may have collided with a foreign ship or with a stray mine.
But it emerged that an explosion was caused by fuel that had leaked from a torpedo.
This started a fire, which subsequently caused all ammunition on board to detonate.
The boat was raised and the bodies recovered in 2001.
At least 77 people have been killed after a lorry loaded with passengers and goods crashed in the Central African Republic, officials say.
[NEXT_CONCEPT]
Twins claim world record title as the first pair to be born in different countries - nearly 40 years later.
[NEXT_CONCEPT]
Leicestershire have signed Middlesex all-rounder Neil Dexter on a three-year contract from the start of next season.
[NEXT_CONCEPT]
Ceremonies are being held in Russia and on board its naval vessels to commemorate the 10th anniversary of the Kursk nuclear submarine disaster.