A male student was in custody but authorities did not release his name or age and said they are still interviewing him. A gun was also recovered at the scene in Homestead, south of Miami, but authorities didn't say where or how many times the victim was shot.
"We still don't know what the motive may have been," said police spokesman Det. Alvaro Zabaleta.
Eight other children, including the victim's 7-year-old sister, were on the bus but were not harmed. Authorities took the children and the bus driver to a police station to be interviewed.
The victim, who has not been identified, attended charter middle school Palm Glades Preparatory Academy. The victim's sister went to nearby Summerville Advantage Academy.
Concerned parents gathered at the shooting site, which was cordoned off by crime scene tape as authorities combed the bus for evidence and gathered children's backpacks and belongings. The shooting occurred about seven minutes away from the school.
Fabian Otero said he was relieved his son Christian, an eighth-grader at Palm Glades, rode to school with his wife. He said he and his wife have been shaken by the killing and are going to discuss enrolling their son in a different school or possibly homeschooling him.
"I was stunned! I was stunned!" he said. "That hits really close to home. That's just scary."
About a dozen parents picked up their children early, said Lynn Norman-Teck, a spokeswoman for Florida Consortium of Public Charter School. Only a throng of TV news crews camped outside signaled the violence from earlier in the morning.
Many of the students had not heard about the shooting and the school did not make an announcement before school was dismissed, but word started to trickle out as they walked outside to waiting school buses.
Thirteen-year-old Eric Carillo said he was in the same class as the victim a few years ago.
"She was a good girl. She was fun," the 13-year-old said.
Sarah Baer said she wouldn't let her daughter walk home from school because there are rough neighborhoods a few blocks away.
"I always take my daughter to and from school. This is so heartbreaking especially right before Thanksgiving," she said.
The school bus was not equipped with video surveillance equipment.
A phone message left for the private school bus company was not immediately returned.
Associated Press writer Matt Sedensky contributed from West Palm Beach.