The bus was carrying Israeli youth, and several surrounding vehicles were also hit by the blast. Israel's Foreign Minister Avigdor Lieberman announced that the deadly explosion was caused by a bomb.
Lieberman said that seven people had died, but Bulgarian officials have put the death toll at six. Authorities said at least 32 people were wounded in the blast.
The explosion took place in the Black Sea city of Burgas, about 250 miles east of the capital, Sofia. The bomb apparently went off at a parking lot at the local airport where the Israeli tourists had just landed.
Israelis often have been targeted in attacks outside their country, and Wednesday's bombing coincided with the 18th anniversary of the bombing of a Jewish community center in Argentina that killed 85 people.
Israeli Prime Minister Benjamin Netanyahu called it "an Iranian terror attack" and promised a tough response. Israel is vowing to strike back at Iran.
President Barack Obama termed it a "barbaric terrorist attack" and called Israeli Prime Minister Benjamin Netanyahu to pledge U.S. help in finding the perpetrators.
Tehran did not immediately issue any comment.
The Associated Press contributed to this report.