The A38 has been closed to traffic in both directions after a crash left "several casualties with serious injuries".
Devon and Cornwall Police have closed a stretch of the road between the roundabouts for the A374 and A388, leading to delays.
Highways England says the incident is not expected to clear until around 8pm.
A Devon and Cornwall Police statement said: "Police were called to reports of a multi-vehicle collision on the A38 at Saltash at around 3pm today (Monday 19 April).
"There are believed to be several casualties with serious injuries, following the road traffic collision.
"A number of road closures have been put in place to allow emergency services to deal with the situation. It is likely to remain closed for some time and members of the public are being asked to avoid the area.
"Devon Fire and Rescue Service and air ambulances from Devon and Cornwall are also attending the scene.
"Both carriageways will be closed to allow the air ambulances to land. The incident is ongoing."
Anyone who witnessed this incident, or who has any information is asked to email firstname.lastname@example.org or call 101 and quote log number 0536 of 19 April 2021."