The city council is to introduce a bus gate at Nelson Mandela Place from midnight on Sunday June 8.
That will mean cars will be banned from travelling into George Square, with only buses, taxis and cyclists allowed access.
Roads bosses say that will result in a 70% cut in the volume of traffic - around 8000 vehicles - moving through Nelson Mandela Place during the day.
The bus gates will operate from 7am until 7pm, seven days a week and will result in a drop in road congestion, a reduction in harmful exhaust emissions and will improve the environment for pedestrians.
It is hoped the scheme will also result in improved bus journey times and reliability through Nelson Mandela Place and George Square.
Motorists will be diverted up Hope Street, along Cowcaddens Road and down North Hanover Street.
The existing taxi rank in Dundas Street will be closed with access restricted to service vehicles only.
A new taxi rank with capacity for nine black cabs, will be created, on Monday June 9, on the south side of West George Street between Buchanan Street and Dundas Street.
All traffic will be banned from the east side of George Square, outside the City Chambers.
The plan is to raise the existing road there to the same level as the square.
Bollards, which can be retracted to allow access for emergency vehicles or VIPs visiting the City Chambers, will be installed at each end of the street.
Alistair Watson, the council's land and environment spokesman, said: "This bus gate is set to 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 the entrance of Queen Street station and better access for buses to the busy stops on the north side of West George Street."