A police spokeswoman said two cars collided on Biggar Road at about 4:40pm and police are still at the scene at 6:45pm.
Details of injuries are not known at this stage but the collision is understood to be serious.
A tweet from the council-run Edinburgh Travel News said three of the approaches have been closed in both directions due to the collision, apart from Frogston Road West.
Their latest tweet says the other three routes at this junction will "remain closed for some time."
Edinburgh Travel said the incident will affect the bypass back to Lothianburn and likely the A702 road.
Local residents have also reported a separate collision, further south on the same road, involving up to four vehicles.
Police said they did not have details on this incident.
The Scottish Ambulance Service has also been contacted.