Frenchman David Friio bagged a double as Paul Sturrock's hot shots hit the goal trail again Plymouth arrived at Hillsborough with 15 goals from the last three games including a 5-1 demolition job against promotion-chasing Port Vale at the weekend.
Chris Turner's Wednesday side threw away early chances and it proved costly as Plymouth, and Frenchman Friio took control.
Argyle, playing the neater football, snatched the lead in the 21st minute with the Wednesday defence caught flat-footed as Steve Adams picked out the unmarked Friio who beat David Lucas with a crisp header from eight yards.
Plymouth almost grabbed a second in the 40th minute. Adams' 20-yard shot took a wicked deflection but Lucas pulled off a spectacular stop to turn the ball round the far post.
Shot-shy Wednesday squandered a chance three minutes later when hard-working midfielder Robbie Mustoe's fierce strike was deflected to Michael Reddy who pulled his 12-yard shot wide of the far post.
Lucas brought off a brave save diving at the feet of Micky Evans as Plymouth broke swiftly minutes after the re-start, but the Wednesday keeper was helpless as David Norris fired in a stinging strike which beat Lucas but crashed against the bar.
Wednesday plunged into deeper trouble in the 61st minute when substitute Paul Smith tripped Norris in the area and Paul Wotton coolly smashed his spot kick past the helpless Lucas.
Friio grabbed his second three minutes later heading in a Wotton cross from Norris' short corner.
Wednesday pulled one back six minutes from time, Grant Holt picking out Reddy, who coolly walked the ball round Luke McCormick before tapping the ball into an empty net.
The Owls were booed off at the final whistle with Chris Turner likely to make wholesale changes for the Bristol City match on Saturday.