Saints thoroughly deserved their victory, with fly-half Ryan Lamb kicking 13 points and Ben Foden and Roger Wilson scoring tries, while Harlequins were left rueing the absence of first choice fly-half Nick Evans and the number eight Nick Easter being sin-binned in the first half.
Saints piled up a decisive 11-point lead with Easter in the sin bin, and Evans's replacement Rory Clegg missed two kickable penalties early in the second half just as Quins looked like mounting a comeback.
It had started well for Harlequins on a cold, clear night in front of 13,459 fans at Franklin's Gardens, and with England's interim head coach Stuart Lancaster in the stands there was plenty of incentive to perform for a number of players hoping to be named in the England Six Nations squad next week.
The opening 10 minutes saw Quins as the more threatening side, but handling and kicking errors halted a number of promising attacks.
Lamb then put Saints 3-0 ahead with a penalty after 12 minutes, before his side took a grip on the match with some compelling forward play.
Pounding at the Quins line, they drew a string of penalties until referee Dave Pearson lost patience with the visitors and sin-binned Easter.
Saints made the most of their numerical advantage, with Lamb slotting a drop goal and Ben Foden scoring a well-taken try wide on the right to extend the lead to 11-0.
Lamb missed the difficult conversion but did add a second penalty just a few seconds after Easter had returned to the field.
Although Clegg pulled a penalty back, Lamb's successful kick on the stroke of half-time saw Saints take a thoroughly deserved 17-3 lead into the break.
Quins started the second half well, but when Clegg failed with two penalties within 10 minutes of the restart, Saints pounced.
A sweeping attack went to the right then back to the left, with number eight Roger Wilson scoring a try which took the match beyond the visitors. Lamb's successful conversion made it 24-3.
Quins had their chance to get back into the match when Saints second row Mark Sorensen was sin-binned just before the hour mark.
But the Premiership leaders failed to score during that period as Saints continued to control the match and produced some ferocious defence when required.
With the match effectively won, Saints went looking for late tries for the bonus point but failed to make the most of opportunities on either wing.
Harlequins also had late opportunities to score but could not find the guile or organisation to break down the Northampton defence.
The defeat was only the second of Harlequins' season and they remain on top of the Premiership table, while the victory means Saints stay third, four points behind second-placed Saracens, who host Bath on Sunday.
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