The crash, involving the tractor-trailer and a car, happened around 5:30 a.m. at Cambridge Road.
According to police a Honda Civic, driven by 29-year-old John Bruecks of West Grove, crossed over the westbound lanes.
The driver of the truck, 58-year-old Dan Wesler from Phoenixville, tried to avoid the car without success.
The impact, along with the evasive maneuver by the truck driver, caused the rig to flip onto its side.
The Honda also overturned, knocking down a utility pole.
Both drivers sustained moderate injuries and were transported to Crozer-Chester Medical Center.
Authorities say some 75 gallons of hot asphalt and 20 gallons of diesel fuel spilled onto the highway.
Route 322 was closed between Route 1 (Balitmore Pike) and Foulk Road.
Route 322 was reopened by 4:15 p.m.