The plane landed in shallow waters and was not submerged, according to the Jacksonville Sheriff's Department. Authorities said all human passengers and crewmembers on board are OK, though at least four pets in the cargo hold are presumed dead.
The flight originated at Guantanamo Bay, Cuba, and was headed to Naval Air Station Jacksonville. That's where the Boeing 737-800 went off the runway and into the St. John's River.
Officials said the flight was contracted by the Department of Defense. It's a regularly scheduled flight for military and civilian personnel. Some were staying in the area, while others were set to fly on to other parts of the country.
NAS Jacksonville said 136 passengers and seven crew members were on board. The sheriff's department said 21 adults, some with minor injuries, were taken to hospitals.
Jacksonville's mayor said President Donald Trump called to offer help as the situation was first developing.
One passenger on the plane said she knew something was wrong the minute they boarded the chartered 737.
"As the plane hit the ground, literally hit the ground and bounced, it was clear that the pilot did not have complete control of the plane because it bounced some more. It swerved and tilted left and right," said passenger Cheryl Bormann.
Bormann told CNN the plane had been four hours delayed and had no air conditioning.
There's no indication of what led to the runway skid, but thunderstorms were reported in the area.
"We were in water," Bormann said. "We couldn't tell where we were, whether we were in the river or the ocean. There was rain coming down, there was lightning and thunder. We stood on that wing for a significant period of time."
A marine unit responded to the scene as passengers said there were animals stuck in the cargo unit that needed rescuing. It's unclear if those animals were saved.
The National Transportation Safety Board and the Federal Aviation Administration will be investigating the crash. Meantime, crews were working to contain jet fuel that was leaking into the river.
As of Sunday afternoon, the flight data recorder had been retrieved undamaged and was on its way to Washington for further examination. The cockpit voice recorder is located in an area of the aircraft that is submerged and cannot be retrieved until the plane is moved.
It's not yet clear how the aircraft will be removed from the water. The airport remains closed.