Northampton skipper Marc Richards swept in Northampton’s second goal on 58 minutes following a slick passing move and after Plymouth failed to clear their lines effectively.
James Collins put Northampton ahead on 38 minutes with a simple tap-in after tackling Plymouth keeper Luke McCormick as he received right-back Kelvin Mellor’s back pass.
Argyle substitute Gregg Wylde slid in to convert Ryan Brunt’s 83rd-minute cross to make it 2-1.
On 36 minutes, McCormick had made a superb diving save to keep out John Joe O’Toole’s thumping 25-yard shot as it skimmed off the muddy Home Park pitch.
In a half of few chances, impressive Town striker Richards went close with an early header from Brendan Moloney’s cross from the right.
Plymouth responded with recalled Reuben Reid’s 21st-minute header flapped over by Town number one Adam Smith.
Argyle’s best spell came following Collins’ opener with in-form target man Ryan Brunt flashing a header just wide from Jake Jervis’ corner.
Ricky Holmes looped a header just wide at the start of the second half, with McCormick beaten.