The bus, registered in North Macedonia, crashed around 2 a.m. and there were children among the victims, authorities said. Seven people were taken to hospitals for treatment.
The cause of the crash was not immediately confirmed, but it appeared that the bus hit a highway guard rail, crashed and caught fire.
Officials said an investigation will be launched.
Bulgarian news agency Novinite said representatives from North Macedonia’s embassy visited a hospital where some of the victims were taken.
Photos taken shortly after the crash showed the bus engulfed in flames with plumes of thick, black smoke rising from the scene.
Bulgarian Caretaker Prime Minister Stefan Yanev visited the site of the crash and told reporters it was “a huge tragedy.”
“I take this opportunity to send my condolences to the relatives of the victims,” Yanev said. “Let’s hope we learn lessons from this tragic incident and we can prevent such incidents in the future.”
North Macedonian Prime Minister Zoran Zaev told Bulgarian television channel bTV that he had spoken to one of the bus survivors.
“One of the passengers told me that he was asleep and woke up from an explosion,” Zaev told bTV, adding that the authorities will gather information that is “important for the families of the dead and the survivors.”
Oliver Varhelyi, a European Union Commissioner, sent his condolences to the families and friends of those affected by the crash.
“Terrible news about the tragic bus accident in Bulgaria in early morning hours,” Varhelyi wrote online. “My thoughts & condolences are with the families and friends of those who died as well as with the people and the authorities of North Macedonia.”
In 2019, Bulgaria, an EU nation of 7 million, had the second-highest road fatality rate in the 27-nation bloc with 89 people killed per million population, according to European Commission data.