The bus overturned at around 4:00 am, the IRNA news agency cited Said Ejraie, the emergency services chief in Darab where the accident occurred, as saying.
Besides the schoolgirls, the other person who died was the driver.
Thirty other people were injured, and 13 of them were in serious condition, according to state television.
Despite its roads being in good condition, Iran has a poor record on traffic safety, with accidents caused by reckless drivers killing thousands of people each year.