Taqele Naiyaravoro and Teimana Harrison both scored twice as Saints' superb start to the Gallagher Premiership season continued on Friday night.
Chris Boyd's men simply blew Harlequins away during the first half, racking up the try bonus point before the break.
Naiyaravoro turned on the power to double up, with Harrison and Mike Haywood, on his first start since last November, also scoring before the break.
Harrison added his second before the end, with Saints having responded after a try either side of half-time, from Cadan Murley and Chris Robshaw respectively.
Murley did get another score back before the end, but it mattered not as Saints secured their third win in as many league matches this season.
Harlequins have still not won in Northampton since 2012, but they were ahead early on thanks to a Marcus Smith penalty, kicked from in front of the posts.
However, Saints were straight back at them and after a lovely move from right to left, including a stunning pass from Rory Hutchinson, Naiyaravoro was typically unstoppable, barging his way over the line in brilliant fashion.
Grayson missed the conversion from the touchline, but he was soon adding the extras to a superb score, which involved some slick offloading work from David Ribbans and Tom Wood.
Grayson added the extras and then a penalty as Quins found themselves with a mountain to climb at 15-3 down with just 15 minutes gone.
It was going from bad to worse for the away side with Saints playing at a pace they simply couldn't live with.
And Naiyaravoro was soon given another chance to go one on one as he pouched a pass and shoved his man away in brutal fashion before diving over in the corner.
Grayson converted to make it 22-3 and Saints were already searching for their try bonus point with just 27 minutes gone.
They only waited another 11 minutes to get it, showing the other side of their game as they kicked to the corner and outmuscled Quins to send hooker Haywood over from a maul.
Grayson hit the post with his conversion, but Saints were 27-3 up, and they had been totally dominant.
Quins almost responded with a try before the break, but full-back Aaron Morris was stopped by a last-ditch tackle from Andy Symons.
However, Quins were able to get the ball down before heading in for half-time as replacement Murley found space and used it to good effect.
But Smith missed the simple conversion to compound Quins' frustration as the end of what had been a really tough half for the travelling team.
Quins started the second half with momentum carried over from the first and immediately put the squeeze on Saints.
Eventually the pressure paid off as a quick tap penalty close to the line allowed skipper Robshaw to go over unopposed.
Brett Herron converted and the gap was cut to 12 points, but Grayson was soon chanelling his inner Jonny Wilkinson as he extended it to 15 with a clever drop goal.
Grayson added a penalty soon after as Saints continued to wrest back the momentum.
And Quins were well out of the game when Hutchinson and Dingwall combined to give Grayson a run to the line. He showed great strength before being hauled down just short, but the ball went wide for Harrison to score.
Grayson converted well and at 40-15 up, the noise levels really started to rise.
Quins did manage to bag a third try before the end as Murley went over, and there was still time for Saints lock Alex Coles to head to the sin bin.
But it mattered not as the black, green and gold gathered a comfortable win that keeps them at the league summit.
Saints: Furbank; Collins, Hutchinson, Symons (Dingwall 57), Naiyaravoro (Sleightholme 66); Grayson, Taylor (Tupai 68); B Franks (Waller 51), Haywood (Van Vuuren 66), Painter (Hill 57); Ribbans, Moon (Ratuniyarawa 57); Wood, Gibson, Harrison (c) (Coles 67).
Harlequins: Morris, Ismaiel, Marchant, Tapuai (Murley 33), Ibitoye; Smith (Herron 51), Landajo (Mulchrone 50); Lambert (Auterac 60), Ella Ella (Baldwin 47), Kerrod (Collier 47); Lewies (Lamb 63), Symons; Chisholm, Robshaw (c), Dombrandt (Bothma 53).