East Sussex Fire and Rescue Service (ESFRS) said crews were called to the scene on the A21 near Robertsbridge during the night just after 1.25am.
A spokesperson said: “We were called to a serious RTC on the A21 at Silver Hill, near Robertsbridge, involving five males where the car hit a tree.
“Crews from two appliances, Battle and Hastings, and one officer worked to extract the passengers with the Air Ambulance, Police and Ambulance services in attendance.
“Please avoid the area.”
The AA said on its traffic alert that the road remains closed due to crash investigation work on the A21 London Road both ways between Church Lane and Silver Hill.
It said a detour is in operation on the B2244 from Sedlescombe to Hawkhurst, and A268 back to the A21 at Flimwell.