The crash happened at about midnight Tuesday on U.S. 131 near Plainwell. Police responded to multiple 911 calls about the driver before the crash.
Police said 29-year-old Jeremy Smeltzer of Portage was driving a pickup truck the wrong way and collided head-on with a car, and both drivers died. An injured passenger from the car was taken to a hospital with injuries that weren't considered life-threatening.
Police identified the car's driver as 21-year-old Jaryd Ford of Plainwell.
The roadway was closed for hours following the crash.