The crash occurred about 2:30 a.m. local time when a Chrysler 300 soared off a service road embankment and struck the truck, which was eastbound on Interstate 94, and then hit a median wall, the Detroit Free Press reported.
"It's almost like that car just drove off that cliff, basically at a high rate of speed," city police Sgt. Michael Woody said.
All three people in the pickup died, along with a passenger in the car, he said.
The victims' names had not been released.
Woody said there were four females in the Chrysler, all believed to be from the Detroit area.
Police said the driver of the Chrysler is believed to be the girlfriend of the driver of another car that was pursuing it, possibly at speeds up to 70 mph, the Free Press said. The second car hit a curb and narrowly averted gong airborne as well.
The driver of the Chrysler was in critical condition and two passengers were listed in temporary serious condition at a Detroit hospital, Woody said.
The boyfriend and another man in the second car suffered minor injuries, the newspaper said.
No charges had been filed in crash.