It happened around 9:30 a.m., Halton police say.
Three workers on Walkers Line were struck near Berton Avenue, but it's too early to say exactly what happened, Sgt. Chantal Corner told CBC News.
"The extent of the injuries is unknown at this time, but everyone is breathing," Corner said.
One person was taken to a local hospital, another was taken to Hamilton General, and a third is being taken by air ambulance to hospital.
Walkers Line is closed between Berton and Const. Henshaw Boulevard in both directions, and likely will be for much of the day.