After a quiet start to the match, it was the visitors that took the lead against the run of play through a Nick Evans penalty, adding his first of two penalties in the first half.
© Getty Images
Samu Manoa put the champions in front with just under half an hour played though when he powered across for the opening try of the night.
James Wilson extended the home side's lead early in the second half, while the visitors' chances of a comeback were dealt a blow three minutes later when Kyle Sinckler was sent to the sin bin for a bad tackle on Manoa.
Tom Wood returned from a spell out with injury, coming off the bench to mark his 100th appearance for Northampton with a try, sealing the win with just over 10 minutes to go.
Harlequins did manage to add a late consolation try, keeping the ball alive to leave Marland Yarde to find a gap with the final action of the match.
The result keeps Saints at the top, while Harlequins sit ninth.