Ontario Provincial Police responded to a collision between several passengers on Highway 12 on Sturgeon Bay just before 7:30 p.m.
According to police, one person died at the scene.
Their identities are withheld until their relatives are notified.
A second passenger was seriously injured and taken to Sunnybrook Hospital in Toronto by Ornge ambulance.
Two other passengers were taken to a local hospital for treatment.
The cause of the collision is unknown.
The junction of Sturgeon Bay Road / Vasey Road and Highway 12 will remain closed for several hours, according to police.
The ramps off Vasey Road from Highway 400 are also closed to assist traffic.
Investigators ask anyone who has information or may have dashboard footage to contact police at 705-326-3536 or 1-888-310-1122. Witnesses can also contact Crime Stoppers anonymously at 1-800-222-8477 (TIPS).