Emergency services were called to Furtherwick Road, Canvey Island, just before 16:15 BST.
Police said they responded to reports of a car "in collision with six pedestrians". Five people have been treated by paramedics.
One is in a critical condition and has been airlifted to hospital in London, while a second was airlifted with a potentially life-changing leg injury.
Essex Police said: "A section of the road is currently closed while officers and paramedics deal with the incident."
The East of England Ambulance Service NHS Trust sent three air ambulances, four ambulances and a number of officers.
It said: "A casualty in a critical condition has been flown to a London hospital. A second casualty with a potentially life-changing leg injury has also been flown to a London hospital.
"One casualty has been taken to Basildon and Thurrock Hospital in a stable condition and two other casualties have been taken to Southend Hospital in a serious condition."