It was the visitors who drew first blood through Sonatane Takulua's converted try, but the hosts roared into life through Rob Buchanan, the returning Mike Brown, and Joe Marchant to lead 27-10 at the break.
And the writing was on the wall for Newcastle when Quins sealed the bonus point just two minutes into the second period - Marland Yarde taking advantage of Brown's searing break - before Mat Luamanu, Danny Care and Tim Swiel put the gloss on a resounding victory for the Londoners.
Fly-half Nick Evans was replaced on the hour mark having landed all eight of his kicks from the tee, while Mark Wilson's second-half try was scant consolation for Falcons.
Newcastle had started brightly and grabbed the first score when Takulua darted onto an offload to touch down under the posts in the fourth minute, for a try which he then converted.
Harlequins responded quickly through an offside penalty kicked by Evans, and when a break down the Quins left almost saw the returning Chris Robshaw over in the corner, Buchanan was given a clear run-in under the posts two phases later.
The home side were soon on the scoreboard again, with Tim Visser finding space on the left and passing back inside for Brown to cross the whitewash after 22 minutes.
A series of penalties saw Newcastle enter the Harlequins half and eventually Takulua's kick made it 17-10, but the 10-point cushion was restored when Juan Pablo Socino saw yellow for a high shot on Evans, who then converted the resulting penalty.
And when Marchant picked a loose pass and charged 50 metres for an interception try with the last play of the half, Quins had a commanding lead.
The home side raced out of the blocks after the restart, Brown making a break and then offloading to wing Yarde who went in under the posts.
Harlequins were looking to keep the tempo high and when Care - returning from Six Nations duty - was taken out early, Newcastle replacement Evan Olmstead was shown yellow.
Unable to get out of their 22, the pressure remained on the Falcons, and they conceded fifth and sixth scores when Luamanu crossed from a driving maul and Care snuck over from close range.
Dean Richards rang the changes and Newcastle began to dominate possession, getting a try through Wilson after a series of close-range rucks.
But Quins went past the 50-point mark with five minutes remaining when Swiel added their seventh after good work from Marchant.