Police said that the gas had leaked from the truck near to a champagne producer's building.
The thick white clouds of heavier-than-air gas lay close to the ground of surrounding streets, leaving some buses, trains and cars unable to move due to the low visibility.
A police car surrounded by thick clouds of CO2 gas in Mainz on Tuesday. Photo: DPA
Local people were told not to go into their basements and to avoid the ground floor if possible, as the colourless, odorless gas can suffocate people if it displaces all the oxygen in a room.
The driver of the truck was slightly hurt by the freezing-cold gas and treated as an outpatient at the hospital.
Police said that the gas leak was "as good as over" and traffic was circulating again by the afternoon.
A firefighter walks towards a cloud of CO2 on the street in central Mainz. Photo: DPA
But firefighters were still checking through basement rooms in the affected area to make sure they weren't filled with gas.
It was not immediately clear whether a technical fault or human error led to the leak. Police have impounded the truck and are investigating.