Luther Burrell, with his fifth score in 13 games since joining from Sale last summer, was the man to lift the tension as he flew over towards the end of the first half.
Burrell’s try was Saints’ first at the Gardens since the win against London Welsh on November 24, a total of 320 minutes of action.
And it gave Northampton the impetus they needed to complete the job against Gloucester as a further score from Alex Waller and eight points from Stephen Myler sealed the victory.
Ryan Lamb, who was replaced by Myler during the second half, also landed eight points against his former club, whose only try came from fly-half Ryan Mills.
The success, which included an impressive performance from England man Ben Foden, keeps Saints top of Pool 4.
And they will now be extremely confident of securing a semi-final spot when they head to Sandy Park to take on Exeter Chiefs on Saturday.
Boss Jim Mallinder signalled his LV= Cup intentions by naming a strong side, which included the likes of Foden and the returning Christian Day, for the clash.
But it was Gloucester who started the strongest in front of a good crowd at the Gardens, winning an early penalty which they kicked to the corner.
It was a statement of intent from the men in electric blue but they wasted the opportunity by knocking on and Saints cleared their lines thanks to some cogent scrummaging.
They were soon on the attack, and after a move which started with captain Phil Dowson stealing a lineout broke down, Lamb kicked Saints into a 3-0 lead.
Lamb wasn’t having the best of days with ball in hand, but his kicking radar was on as he doubled Saints’ lead from the tee.
Gloucester had offered little since their bright start, but a quick break, combined with some poor defending from Saints saw the away side go in front.
Wing Shane Monahan mounted a surge into opposition territory and after the ball was recycled, Mills made the most of the opportunity to touch down.
The fly-half then stepped up to kick his side in front and Saints had been made to pay for some porous defending.
The home side had also struggled at the other end, failing to find a cutting edge, but that was to change six minutes before the break as Lamb teed up Burrell, who flew in to score.
The extras were added and Saints had some momentum heading into the second half, but their passing in attacking positions was not up to scratch.
Stephen Myler and Lee Dickson were introduced to up the tempo and made an instant impact as Saints won a penalty in front of the posts, which Myler landed to make it 16-7.
Mills missed a chance to get Gloucester back in the game, slicing his penalty wide of the posts, but Myler wasn’t about to make the same mistake, as he extended his side’s lead.
And the advantage was to get even greater moments later as quick thinking from Waller saw the prop peel off a maul to dive over the line.
It was a sweet moment for 22-year-old who went some way to making amends for the punch which cost Saints a penalty and Heineken Cup points in Glasgow a week earlier.
Myler added the extras and the game was beyond Gloucester, as Saints introduced young wing Tom Collins for his first-team debut.
The academy graduate didn’t get the chance to seal his first appearance with a try, but the home team had done enough as their pursuit of LV= Cup glory starts to gather speed.
Saints: Foden; Wilson, G Pisi, Burrell (Collins 68), May; Lamb (Myler 55), Roberts (Dickson 55); A Waller (E Waller 74), Haywood (McMillan 74), Mercey (Tonga’uiha 66); Sorenson (Nutley 66), Day; Manoa (Craig 66), Dowson, Oakley.
Gloucester: Thomas (Cook 74); Reynolds, Trinder (Tindall 41), Molenaar, Monahan; Mills, Lewis (Cowan 55); Thomas (Murphy 55), Britton (D’Apice 65), Chistolini (Heard 39); Lokotui (Savage 55), Stooke; Buxton, Hazell, Evans (Moriarty 65).
Referee: Luke Pearce