Touchdowns from Jamie Elliott, Soane Tonga'uiha and Tom May saw them race into a 27-3 lead at the interval, with the rest of their points coming via Ryan Lamb's boot.
The Sharks' only score before the break came through Nick Macleod's penalty and, although they hit back through Rob Miller and Tommy Taylor tries, the Saints held out for a convincing victory.
The match was Sale's first since New Zealander John Mitchell took charge of first-team affairs earlier in the week.
For Northampton, England full-back Ben Foden was making his first appearance since September and he was immediately into the action, running the ball back from an over-hit Dwayne Peel box-kick.
That allowed the visitors to build an early platform and, after a dominant driving maul had been illegally disrupted by the Sharks, Lamb slotted the resulting penalty.
It was all Northampton in the opening exchanges but a bone-crunching tackle by Sam Tuitupou on Dominic Waldouck gave the hosts a much-needed foothold in the match.
And Mitchell's men were the next to threaten when Richie Gray's run and offload sent Cameron Shepherd through.
Although they could not force their way over the line, it was called back for offside and Macleod duly converted the three-point opportunity.
However, Saints regained the lead when good work on the short side sent Elliott away on the left. The wing then showed his immense pace to touch down in the corner, with Lamb adding the extras.
Sale were struggling to deal with the sheer power of the away side's pack and a turnover at the breakdown saw them go in for another converted try when prop Tonga'uiha raced away.
Northampton were displaying the type of clinical play which had been absent in recent weeks and Lamb kicked a drop-goal to extend the advantage to 17 points.
But the visitors were not finished and May rounded off an outstanding half for the play-off contenders when he latched on to a stray pass from Macleod to cross the whitewash.
The Sharks came out revitalised after the interval and reduced the arrears almost immediately when Mark Cueto sent Miller clear.
Their stand-off failed to convert but he added a three-pointer to eat into that deficit further on 50 minutes.
All of a sudden it was the midlands outfit who were making the mistakes. However, they could always rely on their dominant scrum to get them out of trouble.
Although Taylor gained a consolation score for Sale, the hosts remained rooted to the foot of the table.
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