The M74 was closed following a collision, near junction 20 for Eaglesfield, and two air ambulances were seen arriving at the scene.
Traffic Scotland tweeted at 7.05pm that the road would be closed for some time.
Vehicles are reported to have been queued back for over four miles, and were eventually turned around.
Motorists were diverted via the B7076.
A Scottish Fire and Rescue Service spokesman said: “We were alerted at 4.42 pm on Wednesday to a report of a road traffic collision involving one vehicle on the M74 northbound between junctions 20 and 19 near Ecclefechan in Dumfries and Galloway.
“Operations control sent five appliances and special resources to the scene.”