Around 19 tonnes of glue has spread across the A76 at Sanquhar in Dumfries and Galloway, causing the main route between Dumfries and Cumnock in East Ayrshire to close.
The glue container burst when the lorry jack-knifed on the road at 5.30am.
Full diversions are being put in place but motorists are being advised to avoid the area.
A police spokesman said: "The glue container on the lorry has burst and glue spilling is affecting the road surface.
"Road diversions are being put in place, however motorists are asked to avoid the area if possible."