None of Roma’s prior 66 league matches ended goalless, and it took just three minutes for them to take the lead. Donyell Malen went on a mazy solo run before lashing past the helpless Adrian Semper.
Bryan Cristante then almost doubled their advantage with a bullet header from a corner that was well-blocked, as the Giallorossi were purring.
They had to wait until the end of the first half for their second goal, though, as Malen grabbed his brace with a cool finish after Devyne Rensch threaded the ball through.
Lorenzo Pellegrini had smashed the crossbar with a free-kick shortly before, with Pisa really struggling to keep the hosts quiet.
However, Malthe Højholt squandered an opportunity to half the deficit early in the second half, with Mile Svilar equal to his effort from the edge of the box.
It would prove costly as Roma wrapped up the points just a few minutes after, as Matías Soulé fed Malen this time and the Dutchman made no mistake once again by finding the bottom corner for his hat-trick.
Pisa were dead and buried, but Stefano Moreo at least made Svilar work again before the hour mark as he headed towards goal from a free-kick.
Roma understandably took their foot off the gas in the latter stages, with Pisa continuing to search for a consolation goal.
Rafiu Durosinmi tried his luck from range, but his shot was too tame to trouble Svilar, who made sure the visitors have now lost a league-high 14 games without scoring as they remain rooted to the bottom of the table and destined for a swift return to Serie B.
In contrast, Roma won their 14th league match without conceding, a record only bettered by table-toppers Inter Milan (15), as they also maintain their 100% winning record against sides currently in the relegation zone (W5).