It happened around 2:30 Sunday afternoon near the intersection of 4th and Broom streets in Wilmington.
Authorities say a red Chevy Lumina was speeding west on 4th Street when it struck a green Ford Windstar head-on.
The impact of the crash sent the striking vehicle into the air and it rolled over several times before landing on top of three parked cars.
Two men were trapped inside the red van as it caught on fire.
Within 40 minutes, the fire department was able to extinguish the flames and free the occupants.
Both men were taken to an Christiana Hospital in serious condition. A woman inside the minivan sustained non-life threatening injuries.
Police are investigating what sparked the crash.