Just before 1 p.m., the SUV was traveling on southbound I-55 near milepost 198 when it left the roadway, entered a ditch and came to a rest in the river.
The cause of the single-vehicle crash was immediately unknown, state police said.
The driver and passenger were transported to OSF St. James Medical Center with injuries.
Southbound lanes were closed for about an hour.
Pontiac is about two hours southwest of Chicago.