The former Watford, Colchester and Coventry boss, 40, has signed a one-year rolling contract and succeeds Gary Johnson eight months after leaving the Ricoh Arena.
The deal brings to an end a two-week search for a new manager, during which time the Cobblers have been heavily beaten twice under two different caretaker bosses, David Lee and Tim Flowers.
The Cobblers are currently 21st in League Two and just three points above the relegation zone.
Boothroyd, who will be assisted by former Swindon manager Andy King, becomes Northampton's sixth manager in five years, and the seventh appointed by David Cardoza since he became chairman of the club.
Cardoza said: "We are absolutely delighted to have Aidy on board, and that he has agreed to take up the challenge of moving this club forwards.
"We were fortunate to have interviewed a number of excellent candidates. We took on board lots of advice and plenty of opinions from people within the game and the message came back loud and clear that Aidy was the best candidate for the job.
"We were looking for a special type of manager who can succeed in two equally important tasks. We need someone who can work to steer us away from the position we find ourselves in in the short term, and someone who can take the club forward in the longer term.
"From our talks it is clear that Aidy knows the problems we have been suffering and he has done his homework on us. He is a good age, he already has plenty of experience from managing in the Premier League and Football League.
"He knows the challenge ahead of him and he has the hunger and the desire to succeed and follow up the phenomenal success he has already had in his career as a manager."
Source: PA
Source: PA