Argyle left-back Robbie Williams rocked Port Vale with a 30-yard left-foot strike in the 18th minute. But Micky Adams' Vale moved up a gear in the second half with goals from Jennison Myrie-Williams, Ashley Vincent and substitute Ben Williamson.
Home goalkeeper Jake Cole did well to keep out Tom Pope's shot at the start of the second half and Vincent will rue his missed opportunity as the ball fell to him six yards out and he fired high and wide.
However, Vincent made amends by winning a 66th-minute penalty, coolly converted down the middle by striker Myrie-Williams.
Vale winger Vincent fired the visitors 2-1 ahead in the 75th minute after a slick pass from Myrie-Williams before Williamson made it 3-1, converting Doug Loft's 77th-minute cross from the left.
Home skipper Darren Purse thought he had pulled a goal back but his header was cleared off the line by Loft.