The collision, which was first reported on the AA route planner website at 5.22pm, took place between Halland and East Hoathly.
A spokesperson for Sussex Police said: “Emergency services were called to the A22 in Whitesmith, near Hailsham, at around 6.20pm on Thursday (22 August) to reports of a collision between a motorcycle and two other vehicles.
“A Harley Davidson motorcycle was reported to have collided with a silver Mini Cooper and an orange Ford Transit van.
“Its rider – a man from Hailsham in his 30s – was taken to hospital with serious injuries, where he remains.
“No other injuries were reported. Anyone who witnessed the incident or has any relevant dashcam footage is asked to contact [email protected], quoting Operation Rumsen.”