The school bus overturned in the collision, and police say several of the 46 children on board were ejected from the bus following a collision with a dump truck.
At least two children have been left in life-threatening conditions.
The crash took place at around 10:30am local time (3.30pm BST) on I-80 westbound near Exit 25 and Route 206.
The cabin of the bus appears to have been completely ripped off the chassis in the horror crash.
NBC New York has said at least one child and one adult have been killed.
NBC
Saint Clare's Denville Hospital and Dover Hospital emergency departments have so far received a total of 10 patients, the network reports, though there was no immediate information on the extent of their injuries or their ages.
And Elaine Andrecovich, a spokeswoman for Morristown Medical Center in Morristown, New Jersey, told CNN:“We are receiving patients.”
She did not confirm whether these were children or adults however.
Images of the scene show a number of people gathered at the site of the collision, appearing to tend to the injured.
NBC
It's a horrific scene
NBC New York reported that the bus, which has the Paramus Board of Education logo on the side, came from East Brook Middle School in Paramus, a public school serving roughly 650 students in grades 5-8.
The school's calendar shows a scheduled fifth-grade class trip to Waterloo Village in Stanhope.
Mayor of Mount Olive Rob Greenbaum said: "There's an incredible emergency response from throughout Morris County and by State Police. It's a horrific scene.
"Obviously my heart goes out to the community and the parents."
NBC
He said he had been told by emergency services that people had been thrown from vehicles as a result of the accident, but he could not tell whether the bus was one of these.
The bus appeared to be owned by the Paramus Board of Education, he confirmed.
Paramus is a borough in Bergen County, New Jersey.
Mount Olive Police tweeted: “Crash investigation on Route 80 by mile marker 25. Route 80 closed both directions.
“Westbound traffic being diverted at exit 26. Expect heavy traffic and delays on Route 46.”
The I-80 has been closed in both directions.
New Jersey State Police tweeted: "#NJSP investigating serious MVA westbound on I-80 @ MP 25 in Mount Olive Twp, Morris County involving a school bus and dump truck.
"All lanes shut down. No further information available at this time. #Alert"
More to follow...