Witnesses said a car with two men inside approached the victims' vehicle and started shooting, Ekathimerini reported. The body of a 38-year-old man was found inside the victims' car and a 31-year-old man was nearby, mortally wounded.
Police said at least 10 bullet casings were found in the area.
Two men were killed Tuesday outside a Patras nightclub by two men on a motorcycle.
Patras, the center of Greece's third-largest metropolitan area, is on the Adriatic coast of the northern Peloponnese, 134 miles west of Athens. A major port since classical times, it is the Greek terminus for most ferry service to Italy.