The section of London Road, near the new Sir Chris Hoy Velodrome, is off limits in both directions as engineers attempt to repair the damage to the collapsed sewer and the road surface above.
An abandoned underground rail tunnel is also being investigated as a potential cause of the collapsed road.
Strathclyde Police said the road had been shut off between Clyde Gateway and Springfield Road, which takes in Celtic Park.
There is still access to the stadium, but drivers have been warned to prepare for congestion in the Gallowgate diversion route.
Police said emergency services were at the scene and that it was unclear how long the road will be closed for.
The diversions may also affect traffic coming off and on to the M74 at Junction 2a Fullerton Road.
A Scottish Water spokesperson said: "Scottish Water is one of a number of utilities working to ensure the integrity of infrastructure in London Road."
Scottish Water has contractors on site to bypass the sewer and ensure there is no environmental impact.
There are also specialists in place to maintain water supply to nearby properties.
Another possible cause of the collapsed road surface is an unused railway tunnel which runs under the street.
However, engineers are investigating the tunnel and it is thought it is unlikely to have been the cause.