"There was an altercation that initially started between two people, and my understanding is that additional individuals joined in against the one person," said Gary Fullman, chief of staff to the Wilmington mayor.
The student was badly injured and transported by helicopter to A.I. DuPont Hospital for Children, where she died, Fullman said.
The fight broke out about 8:15 a.m. as classes started, in a bathroom on the main floor of the school, principal Stanley Spoor said at a news conference. He didn't say what caused the fight.
Two students are being questioned by Wilmington police, he said. No charges have been filed yet, authorities said. Wilmington Police Chief Bobby Cummings said it's not believed a weapon was used.
The name of the victim, a sophomore, has not been released. An autopsy will determine the cause of death.
Students at the school were kept in class until 10:15 a.m. and sent home for the day, school officials said. Robocalls were sent to family members, who rushed to pick up their children. Some of them said they didn't know exactly what had happened.
"They said there was a fight," Denise Dinkins told CNN affiliate WPVI
. "I don't know. I am just trying to find my grandson."
Classes will be held Friday morning but school will be dismissed at 11:15 a.m.
Grief counselors and mental health teams will be available for students "so they have an opportunity to process prior to the weekend break," said Kathy Demerest of the New Castle County Vocational Technical School District.
City officials expressed sorrow at the violence.
"My heart is broken," Wilmington Mayor Dennis Williams said at the news conference. "I am so upset that a young lady lost her life today. Things like this shouldn't happen. My heart bleeds for the family, the kids who go to this school and the administrators, and our city."
"This is not only an unspeakable tragedy for her family, but also for the school, and the entire community," said a statement on the school district website.
"We express our prayers and deepest sympathy to her family, who need your support and sensitivity at this time."