Luke Cowan-Dickie rumbled over for a hat-trick of tries as Exeter Chiefs returned to form after fighting off a late comeback attempt by Harlequins.
The Chiefs had lost both their opening two Aviva Premiership Rugby games - to Saracens and Wasps - but the result was rarely in doubt after Cowan-Dickie and Lachie Turner notched try-doubles in a first half that gave Sandy Park plenty to cheer about.
Rob Buchanan had hit back for Harlequins before the break while Tim Swiel also hit two penalties, but upon Cowan-Dickie's third in the 48th minute it looked game over.
However, the visitors hit back through Danny Care and Charlie Walker, and the Chiefs had to see the game out with 14 men after Tomas Francis was sent off in the closing stages.
Chiefs, Aviva Premiership Rugby Finalists last year, were looking to avoid successive defeats at Sandy Park for the first time since September 2014 - and started as if they had a point to prove.
After a threatening maul was dealt with by Harlequins, Don Armand made the crucial break before Turner rumbled over the line following a series of pick-and-goes.
Gareth Steenson could not add the extras and it was instead Swiel's boot who nudged Harlequins ahead, as he duly punished a couple of Exeter infringements.
But Chiefs recomposed themselves after that series of errors and Ian Whitten nearly provided their second try of the day before being bundled into touch.
They did however capitalise on a Harlequins mistake shortly after, as Buchanan overthrew a lineout and from ten metres out Cowan-Dickie beat Luke Wallace and applied the finish. This time Steenson was on target with the extras.
The alarm bells started to blare even louder for Harlequins in the 20th minute - the hugely impressive Turner running in from some 30 metres out after Olly Woodburn's superb break and offload caught the visitors flat-footed.
Steenson's conversion extended the scoreline out to 19-6, though the third try was seemingly the jolt that Harlequins needed.
Moments after Marland Yarde nearly turned Danny Care's grubber into a try, Buchanan atoned for his errors from the line-out by touching down off the back of a maul. Swiel converted and suddenly it was a one-score game.
Unfortunately for Harlequins, in general Exeter's forwards were very much on top and in a flash a scrum penalty turned into another rolling maul from which Cowan-Dickie grabbed his second of the day.
The hosts ended the half camped on Harlequins' line, and though no try was forthcoming, Steenson opted to kick a penalty that sent Exeter 16 points clear at the break.
Another lineout miscue put Harlequins under immediate pressure in the second half and after prop Kyle Sinckler was pinged for collapsing a maul, the Chiefs went again from the set-piece.
This time the maul made its way over and Cowan-Dickie was the beneficiary once more to complete his treble, and Steenson made no mistake with the extras.
To their credit, Harlequins showed no signs of giving up and reignited hope with 15 minutes to go when Danny Care dashed through following a Mike Brown off-load.
A try-bonus point at the very least was then on for the away side when Marland Yarde and Charlie Walker combined for the latter to cross, though Swiel failed with the conversion.
With eight minutes to go, Francis was sent off for foul play in a ruck but Exeter got home and hosed.