The crashes happened in the westbound lanes of the highway near Lake Michigan Drive NW in Grand Rapids.
State police said a vehicle carrying four people was traveling west at a high rate of speed when the driver lost control of it and struck the right guard rail. That vehicle came to rest in the left lane of the highway.
A second vehicle stopped on the right shoulder to help the driver of the first vehicle. A third vehicle then swerved to avoid the good Samaritan and hit the vehicle that was stopped in the left lane.
The Holland teenagers in the first vehicle were pronounced dead at the scene. A third person was taken to Spectrum Health Hospital in Grand Rapids with injuries. A fourth person fled the scene on foot and has not been located, according to police.
The driver of the third vehicle suffered minor injuries, police said.
The driver of the first vehicle, Julien Alexander Tirado, 17; and a passenger, Kevin Singnoy Boonheaun, 17, were killed in the crash. The others involved in the crash have not yet been identified.
The four-door Honda that Tirado was driving is owned by a relative identified by the Michigan Secretary of State as Carmen Tirado, 51.
The westbound lanes of I-196 were closed for about four hours after the crash.