Houston Fire Chief Samuel Pena said the crowd that had gathered for a performance by rapper Travis Scott began to push towards the front of the stage about 9pm on Friday, causing panic and injuries.
People began to fall unconscious, and the mayhem escalated at NRG Park until 9.38pm when a "mass casualty incident" was triggered, he said.
The fire department transported 17 people to hospitals, and 11 of those transported were in cardiac arrest.
It was not yet clear what caused the disaster.
"I think it's very important that none of us speculate. Nobody has all the answers tonight," Houston Police Chief Troy Finner said.
"If you don't have facts, if you don't have evidence, I'm not going to speak against that. We have hurting families out here."
Finner said the organisers and Scott were co-operating with police.
Live Nation, the event organiser, and Astroworld did not immediately respond to a request for comment.
"It happened all at once. It seemed like it just happened ... over the course of just a few minutes," Houston Police Executive Assistant Chief Larry Satterwhite said.
"Suddenly we had several people down on the ground, experiencing some type of cardiac arrest or some type of medical episode."
The Houston Chronicle said Scott stopped multiple times during his 75-minute performance when he saw fans in distress near the front of the stage.
He asked security to make sure they were OK and help them out of the crowd. Emergency vehicles, lights and alarms flashing, cut through the crowds several times.
The fire department said on Twitter that a reunification centre had been set up for families who had not heard from loved ones at the festival.
A crowd of 50,000 showed up for the two-day event, Pena said. The second day of the festival has been cancelled.
"(It's) obviously a very extremely tragic night. Our hearts are broken," Harris county judge Lina Hidalgo said.
"Tonight's focus though needs to be on the families and on the lives that we've lost. Many of them extremely young, tragically young."
