The crash, near Dryons on Shaftesbury Junction, happened at about 10am.
At least two ambulances were called to the crash, which an eyewitness said involves a van and a bus.
Nick Bell, who walked past the scene at 10.20am, said: "The van has quite a bit of damage to the rear and the bus to the front.
"There was glass all over the junction and it looks to be awaiting recovery."
There are long delays on York Road (A64) eastbound heading out of Leeds, as one lane remains blocked as the vehicles await recovery.
Pictures show traffic at a standstill, queuing back towards Leeds city centre. There are delays to First Bus services.