Michigan State Police said roughly a dozen people were injured, but no one was killed in the crashes on westbound Interstate 196 in Hudsonville, Michigan, just outside of Grand Rapids.
I-196 was closed between 32nd Avenue and 64th Street for hours before reopening.
The Ottawa County Sheriff's Department is investigating the crashes, which took place around 10:20 a.m.
Motorists in the area are encouraged to avoid travel.
Temperatures are frigid throughout much of the Midwest Monday.
Lake-effect snow also caused whiteout conditions near Grand Rapids earlier Monday.
Indiana State Police said multiple vehicles were involved in a crash on the Indiana Toll Road, as well.
Both eastbound and westbound lanes were closed but have since reopened. The crashes occurred in the westbound lanes between mile markers 67.1 and 67.2.
Indiana State Police say blowing snow reduced visibility, which led to the chain-reaction crash that halted traffic in both directions.
Some injuries have been reported, but none are believed to be life-threatening.
The incident happened just before noon Monday in St. Joseph County, Indiana.
ABC News contributed to this report.