Eyewitness said flames were "shooting 30ft in the air" after the collision on the southbound carriageway of the M40 in Warwickshire.
Dramatic pictures show the inferno and the silver Audi car and Mercedes van covered with white foam after the flames had been extinguished by firefighters.
The crash occurred near Leamington Spa just after 7.30am, causing chaos for commuters during the Monday morning rush hour.
A spokesperson for West Midlands Ambulance Service said: "On arrival, crews discovered a car and a van that had been in collision, both of which had caught fire as a result.
"Thankfully, the occupants of all vehicles had managed to get themselves out, otherwise it could have been a very different outcome.
"A man and a woman from the car, together with two children, were all assessed and discharged at the scene with minor injuries, as was the man who was driving the van."
Police called all three lanes of the M40 after the crash which happened between junction 13 for Bishops Tachbrook and junction 12 for Gaydon.
A spokesperson said: "Road users are strongly urged to consider alternative routes and to allow plenty of additional time for their journey.
"If feasible, please consider delaying your journey until the incident has been cleared and the delays have eased.
Meanwhile two people died after a single car crash on the M6 in Warwickshire at 1.50am.
The male driver and female passenger were declared dead when emergency services arrived at the scene on the southbound carriageway near Corley Service Station.
Warwickshire Police said they believe they have identified the driver as a man from Coventry, while enquiries are continuing to identify the woman.
Inspector Lucy Sewell said: "Following our initial enquiries we believe we have identified one of the occupants of the car and we are in the process of informing their family.
"We are currently carrying out enquiries to identify the passenger."
West Midlands Ambulance Service was called to the southbound carriageway of the motorway between junctions four and three, near to Corley Services, just before 2.15am.
An ambulance and a paramedic area support officer attended the scene.
A West Midlands Ambulance Service spokesman said: "On arrival, crews discovered two patients in the car, which had set alight.