In shocking video from the scene, hundreds of people swarm the truck, with some clinging to the cab, as it comes to a stop.
The driver appears to be then dragged out, with police confirming he has now been arrested.
Highway 35 West had been closed to traffic for nearly an hour when the incident unfolded on Sunday around 6pm, with people desperately scattering out of the way.
The truck reportedly belongs to a cement company from Michigan and had come from Canton, Ohio.
Minneapolis police closed in and took the driver, who was reportedly injured, into custody.
Up to 5,000 people are estimated to have been involved in the protest at the time.
Witness Melanie Ramos told the Star Tribune: "A truck came. The horns were blaring. It was picking up speed. It was plowing down the highway into the protesters. It was the most terrifying thing I've ever seen."
Minnesota Department of Public Safety tweeted: "Very disturbing actions by a truck driver on I-35W, inciting a crowd of peaceful demonstrators.
"The truck driver was injured & taken to a hospital with non-life threatening injuries.
"He is under arrest. It doesn't appear any protesters were hit by the truck."
