Delaware State Police responded to the scene north of Route 40 just after 1:00 p.m.
According to police, a 1995 Jeep Wrangler was traveling backwards on southbound Route 1 when it struck the driver's side of a southbound 1998 Audi A4.
The impact forced both vehicles off the roadway.
Witnesses at the scene performed CPR on the driver of the Jeep, identified as 54-year-old James T. Holland of New Castle, until emergency crews arrived. Holland was resuscitated and then transported to Christiana Hospital, where he was admitted in critical condition.
The driver and two passengers in the Audi were taken to Christiana Hospital for treatment of various injuries. A third passenger in the Audi, identified as Douglas M. DiSabatino, 19, of Bear, was admitted to Christiana Hospital in critical condition.
Delaware State Police are continuing to investigate what led to the crash.
There is no word yet on why Holland's jeep was traveling in reverse.