Tigers flew into a 27-0 lead inside the opening 35 minutes, bagging the try bonus point in the process as they called the tune early on against Chris Boyd's side.
Saints eventually came to life with a Courtnall Skosan score just before the break, and they threatened early in the second period, with Tigers reduced to 13 men due to two yellow cards.
Alex Mitchell scored but it wasn't enough to provide a stable platform as table-topping Tigers managed the game and then put their foot on the accelerator once more.
George Ford was at the heart of it all as he notched 20 points with the boot, taking advantage of a string of errors and penalties conceded by Saints.
Skosan did snatch a try bonus point late on for the hosts, adding to Mitchell and Alex Waller's second-half efforts, but Tigers still had time to score yet again through a Jack van Poortvliet interception.
Ford finished the day by putting the ball between the posts as Tigers savoured a day to remember and Saints reflected on one to forget.
The signs had been ominous from the off at the Gardens as former Saints prop Francois van Wyk had an early impact, winning a penalty, which Ford slotted with ease.
It was a frantic start, as expected, but Tigers were the ones firing the shots early on.
Saints had a penalty reversed after Api Ratuniyarawa was punished for a late hit on Dan Cole, and the away side built from there, scoring the game's first try, through Nemani Nadolo out wide.
Ford missed the conversion and Dan Biggar soon sent an effort of his own wide of the posts at the other end after Saints had secured a penalty.
Tigers were in control of the game though, applying real pressure, and as Saints continued to ship penalties, the away side pounced again.
Some patient play resulted in a score for van Wyk, who celebrated a score on his first return to the Gardens.
Ford converted and it was 15-0 after just 20 minutes, with Saints already in real trouble.
And things got even worse soon after as Alex Mitchell knocked on and Nadolo gathered, even having time to slip before scoring in the corner.
Ford hit the post with the conversion but the gap was 20 points and the hosts were staring down the barrel of a disastrous defeat.
Nothing was going well for the hosts, who were soon deep inside their own half once again, giving away penalty after penalty as Leicester put together a series of lineout drives.
Eventually Julian Montoya went over for the Tigers, bagging the bonus point inside just 35 minutes.
Ford rubbed salt in the wounds with the conversion and there was sheer deflation inside the Gardens.
But there were finally signs of life on the stroke of half-time as Skosan skated over out wide.
Biggar was unable land the conversion with the final kick of the first 40 minutes and the players trotted off to near silence in front of a stunned home crowd.
Saints were forced to withdraw Biggar at the break as he looked to have sustained an injury, meaning James Grayson came into the action.
Grayson was soon booting the ball to the corner after Richard Wigglesworth was sin-binned for contact with the head of onrushing Fraser Dingwall.
And Saints soon profited as Dingwall made a big carry and Mitchell spotted space to score.
Jasper Wiese was yellow carded for a no-arms tackle in the build-up, reducing Tigers to 13 men and providing new hope for Saints.
Grayson delivered an incredible 50:22 to pile more pressure on Tigers before Mitchell was held up over the line as Saints surged forward.
But the hosts just couldn't make their rivals pay as Tigers managed the game and were winning the the double sin-bin period 3-0 after a sublime drop goal from Ford.
However, Saints hit back, finding numbers on the left, allowing Waller to score.
Grayson converted and it was an 11-point deficit with 22 minutes remaining.
But Tigers hit back almost immediately, winning the breakdown battle once more, giving Ford another three points from the tee.
Ford notched another penalty soon after as the game continued to get away from the sinning Saints.
It was just blow after blow landed on the Saints chin, and another one left Rory Hutchinson on the canvas as his attempted clearance was charged down by van Poortvliet, who scored.
Ford converted to make the scoreline an eye-watering 43-19, and the points kept coming as Kini Murimurivalu ran through two Saints players to score.
Saints responded with Skosan finishing things off after a tidy crossfield kick from Grayson, giving the hosts a try bonus point.
But Tigers had the final say as van Poortvliet intercepted and scored, allowing Ford to put the icing on the cake with the conversion.
Saints: Hutchinson; Skosan, Proctor, Dingwall, Collins (Litchfield 50); Biggar (Grayson 40), Mitchell (Lomani 68); Waller (c) (Auterac 59), Matavesi (Haywood 59), Painter (Hill 45); Ribbans, Ratuniyarawa (Moon 64); Wood (Coles 56), Harrison, Augustus.
Leicester Tigers: Burns (Hegarty 66); Potter, Moroni, Kelly, Nadolo (Murimurivalu 64); Ford (c), Wigglesworth (van Poortvliet 64); van Wyk (Leatigaga 66), Montoya, Cole (Heyes 66); Wells (Cowan-Dickie 61), Snyman (Green 45); Chessum, van Staden (Reffell 50), Wiese.
Referee: Tom Foley