New traffic rules will cut the number of vehicles using the historic square by up to 70%.
Roads bosses plan to install a bus gate to bar private cars from Nelson Mandela Place and West George Street.
In future, only buses, taxis, private hire cabs and cycles will be able to use the route.
Motorists are likely to be diverted up Hope Street, along Cowcaddens Road and down North Hanover Street.
Roads bosses also plan to ban all vehicles, except cycles, from the section of George Square in front of the City Chambers, with the existing road raised to the same level as the Square.
Bollards will be installed at each end of the street, which will be able to retract to allow access for emergency services or VIPs visiting the City Chambers.
The existing taxi rank will be banished from Dundas Street, with access restricted to delivery vehicles.
That taxi rank will be relocated to the south side of West George Street. The new rank will be able to accommodate nine cabs.
The direction of service vehicles in Buchanan Street will be reversed between Bath Street and Nelson Mandela Place and between St Vincent Street and Nelson Mandela Place.
And a tourist coach drop-off area will be provided on Cochrane Street.
Roads bosses say the changes will result in a cut in harmful traffic emissions and improve the environment for pedestrians.
The public has until Friday, September 13, to lodge any objections to the new traffic restrictions.
Alistair Watson, the city council's executive member for land and environmental services, said: "This bus gate will see a reduction of around 70% in the current level of traffic.
"As a direct result, there will be a substantial reduction in the degree of congestion and vehicle pollution in the area.
"The reduction in traffic will also lead to improved pedestrian access to Queen Street Station and better access for buses to the busy stops on the north side of West George Street."
Stephen Flynn, vice-chairman of Glasgow Taxis said: "We welcome any initiatives which ease the flow of traffic in the city centre.
"We continue to call for more taxi ranks in the city centre, helping to get people home quickly and safely."
Neil Greig, of the Institute of Advanced Motorists, said he was concerned the new traffic rules would result in congestion in other parts of the city.
And he questioned whether the changes would have much impact on pollution.
Mr Greig said: "The council is trying to develop the area as a pedestrian location but often these things have unintended consequences.
"They need to very carefully monitor where the traffic is going and any congestion problems.
"In my view, most of the pollution comes from vans, lorries and buses belching out diesel fumes.
"I don't see removing private cars from the city centre will make that much of a difference."