Images of the buckled structure at the college in Miami were shared across social media on Thursday afternoon.
A Florida Highway Patrol official said there were several fatalities, but police have yet to confirm a number.
It was unclear how many people were still trapped in eight vehicles beneath the bridge, Miami officials said.
"This is going to be a long incident. We are going to have rescuers here through the night, if not longer," Miami-Dade Fire Chief Dave Downey said on Thursday.
At least eight people have been taken to hospital to be treated for injuries. Two people were "cut out and extricated from the debris", he added.
Florida Highway Patrol Lt Alejandro Camacho told CBS News there were several fatalities.
US Senator Bill Nelson told local media six to 10 people were killed in the collapse, but the exact figures have yet to be confirmed by law enforcement.
Aerial footage shows first responders trying to get under the bridge to trapped cars.
The university issued a statement saying rescue efforts were still underway.
"We are shocked and saddened about the tragic events unfolding at the FIU-Sweetwater pedestrian bridge," said a university spokesperson.
"At this time we are still involved in rescue efforts and gathering information."
Miami-Dade County Emergency Management urged commuters to avoid the area.
A witness told ABC News that the screams coming from the cars were "terrifying".
"As soon as I looked outside, I saw dust flying everywhere," Tiona Page said. "I knew the bridge had collapsed."
Another witness, Damany Reed, told CBS News: "I heard a big kaboom...it sounded continuous. We look outside...we thought something had fallen but it was the bridge that collapsed. It was just surreal at that moment and pretty scary".