It happened at 9 p.m. near Interchange 9 in the outer roadway in the truck lanes.
Bus is operated by a company called Super Luxury Tours out of Wilkes Barre, PA.
There are at least two people dead and at least five others in critical condition.
They were rushed to Robert Wood Johnson Hospital in New Brunswick.
ABC News is reporting that the bus was headed from Chinatown to Philadelphia.
The bus struck a New Jersey Turnpike guard rail on the left side of the highway. It then hit a concrete abutment and went straight back across the road and slid off the right side.
The driver reportedly was ejected through the front window. His condition is not yet known.
20 of the bus passengers are uninjured and on the side of the road waiting for another bus to come pick them up.
Two southbound outer lanes are closed with emergency vehicles.
There were 40 people on board. All of those on board were transfered to the hospital for evaluation.