The collision, involving the pedestrian and a blue BMW M3 convertible, happened shortly after 11am.
Isle of Wight police and paramedics were called to the scene, and the north bound carriageway has been closed between Coppins Bridge and St Mary's roundabout.
A spokesman for the Isle of Wight NHS Trust confirmed the pedestrian, a middle-aged man suffered serious injuries and would be transferred by air ambulance to Southampton General Hospital.
A police spokesman said the north bound carriageway was likely to remain closed for the next four hours. Diversions have been put in place but drivers are advised to avoid the area.
It was initially reported the man had suffered potentially life-threatening injuries, due to information supplied, however a police spokesman confirmed at around 3pm the man's injuries were serious, but not life-threatening.
"Police are appealing for other drivers to come forward following a serious injury road traffic collision involving a pedestrian and a car on the A3054 Medina Way at just after 11am this morning.
"The pedestrian, a 35-year-old man from Cowes was seriously injured in the collision also involving a BMW M3.
"He has been taken to Southampton General Hospital to be treated for serious and life-changing, but not life-threatening, injuries to his arm and leg. No-one else was injured.
"Police officers are now carrying out an investigation at the scene and a section of the dual carriageway will be closed for at least 4 hours. Diversions are in place and Hampshire Constabulary would like to thank motorists in the area for their patience following this serious incident.
"Traffic is already heavy in the area, we would advise motorists to avoid Medina Way and adjoining roads for the time being.
"If you are on the road please ensure you stay hydrated during the hot weather, as your journey may take longer than expected. Hampshire Constabulary is working in partnership with Island Roads (follow @Islandroads on Twitter) to keep congestion to a minimum this afternoon," he said.
Police asked witnesses to contact Sergeant Dave Sanderson at Shanklin Roads Policing Unit on 101 quoting 44140264840.
You can also call the charity Crimestoppers line on 0800 555 111 where information can be left anonymously.
*The northbound side of the dual carriageway re-opened at around 3.30pm, according to Island Roads.