Bondz N'Gala gave Plymouth a 12th-minute lead, beating Nicky Weaver with a low drive from just outside the area after Kari Arnason's cross was only half cleared.
Wednesday went close to equalising when Gary Teale's strike came back off the crossbar, but Mason increased Plymouth's lead from close range after Carl Fletcher's cross was headed down. Onismor Bhasera failed to capitalise on a defensive lapse from Reda Johnson as he fired straight at Weaver.
After referee Iain Williamson waved away two penalty appeals from Wednesday, substitute Giles Coke pulled a goal back for the home side, smashing a superb 20-yard effort past Romain Larrieu.
But Mason restored Plymouth's two-goal advantage four minutes later, producing a fine finish from just inside the area for his second of the match.
Yannick Bolasie made it 4-1, lashing a low 30-yard drive past Weaver before Johnson headed a second goal for Wednesday against his former club.