Witnesses said Susan Jordan managed to push several children out of harm's way before she was hit.
Two 10-year-old students have been hospitalised with serious but non-life threatening injures.
Indianapolis Fire Department said the bus was one of several lined up outside the Amy Beverland Elementary School when it suddenly lurched forward and mounted a curb.
The female bus driver told firefighters she is not sure what caused the bus to accelerate.
Police Sgt. Kendale Adams told reporters that the crash appeared to be a "freak accident".
In a statement on its website, the school said: "District-wide, we will mourn the loss of our beloved Susan Jordan, principal of Amy Beverland Elementary."
The school board, meanwhile, described Mrs Jordan, who had been head teacher at the school for 22 years, as an "amazing educator".
"She had a remarkable way of making everyone she came in contact with feel valued and important. She had a passion for children that is unmatched," the board said.
In May 2015 fellow colleagues and students published a moving video on YouTube thanking Mrs Jordan for all her work.
The video ends with text saying: "We love you, Mrs. Jordan! Amy Beverland really is the sunshine after the rainbow. Thank you for your many years of leadership!"
Neither the driver or any of the 25 children on the bus were injured in the crash, according to US media.
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