The win at Sixfields followed on from the Pilgrims’ impressive 4-1 home success over Carlisle United on Tuesday.
Once again summer signings Graham Carey and Jake Jervis were their key men.
Carey gave Argyle the lead in the 39th minute when he robbed Northampton and headed for goal before calmly slotting the ball past home goalkeeper Adam Smith.
Jervis then sealed the win in the 71st minute when he pounced on a loose ball following a Carey corner.
The one concern for manager Derek Adams was a first half injury to striker Reuben Reid.
Leyton Orient are the only team who still have a 100 per cent record in League Two. They sit top with Wycombe second and Argyle, who have three wins from four, third.