The A271 in Ninfield, near Ashburnham Place, is closed, following reports of a serious collision involving two motorcycles and a car.
Sussex Police said officers were called around 10.25am.
A spokesperson said: “One motorcyclist has been taken to the Royal Sussex County Hospital in Brighton with serious injuries.
"No other serious injuries have been reported at this time.
“The road is currently closed in both directions. Anyone who witnessed the collision is asked to email [email protected] or call 101 quoting Operation Aveley.”
Meanwhile, another road closure was in place following a two-vehicle collision on the A27 near Firle around 12.15pm.
The road was closed both ways from the Ripe turn-off to Station Road (Drusilla's roundabout), affecting traffic between Lewes and Polegate.
A police spokesperson said: “No serious injuries have been reported.
“The road was blocked temporarily while recovery of the vehicles was arranged. It has since reopened.”