A stretch of Highway 6 through Flamborough was closed for several hours on Wednesday.
Provincial police shut down the roadway between Concession 8 and Safari Road.
It follows a serious five-vehicle crash, and both Hamilton Police and provincial police were called in.
OPP confirmed a 24-year-old from Hamilton was pronounced dead at the scene.
Four others were transported to hospital with various injuries.
The investigation is ongoing. Highway 6 fully reopened Wednesday night.