Just weeks on from putting six past West Ham United without reply, another first-half obliteration saw Declan Rice, Gabriel Martinelli, Kai Havertz and Martin Odegaard register for Mikel Arteta's men, who also benefitted from a Jayden Bogle own goal.
Chris Wilder's abysmal charges entered damage limitation mode in the second half, but Ben White managed to get his name on the scoresheet too, as Arsenal became the first team in England's top four tiers to win three successive away league games by at least five goals.
The first warning sign for Sheffield United arrived just two minutes in, as Saka rattled the crossbar with a close-range shot at Ivo Grbic's near-post, before the Croatian stopper denied Martinelli on the follow-up.
However, Grbic was powerless to prevent the floodgates from opening in the fifth minute, as after some smart link-up play from Jorginho and Martinelli on the right, Rice advanced to the byline and cut back for Odegaard - via the help of a slight deflection - and the Norwegian found the net with a simple side-footed finish.
The captain's opener would be a harbinger of doom for the Blades, who found themselves two down in the 13th minute as Saka soared past former teammate Auston Trusty and fizzed a cross into the six-yard box, where Bogle inadvertently back-heeled the ball into his own net.
Another two moments passed before the men in yellow and black had their third, as after a rapid counter-attack, Martinelli played a one-two with Jakub Kiwior and saw his curling shot creep in at the near post; Grbic was deceived by a nick off of the legs of Anel Ahmedhodzic.
Martinelli's effort was the 300th Premier League goal Arsenal have scored under Arteta in his 161st top-flight game in charge - only Pep Guardiola (120), Jurgen Klopp (142) and Manuel Pellegrini (149) achieved a treble century in quicker time - and with the Trusty left-back experiment ending in disaster, a stone-faced Wilder brought on Ben Osborn for Oliver Norwood in a 16th-minute tactical change.
A rare Blades venture into the Arsenal half in the 20th minute saw James McAtee cut inside and let fly, but his long-range drive sailed into the Arsenal crowd behind David Raya's goal, who would soon be celebrating their side's fourth at the other end.
Pleas from Ahmedhodzic for a foul by Havertz fell on deaf ears - the Sheffield United captain then threw Martinelli to the floor out of pure frustration - but referee Sam Barrott played advantage, allowing Havertz to advance into the box and find the far side of the net with a crisp finish across Grbic's goal.
Fans had already begun to stream out of the stadium before the German made it three goals in three Premier League games, but those that stayed saw Gustavo Hamer set away for a one-on-one with Raya in the 26th minute, but the Brentford loanee came up trumps before the offside flag went up.
Arsenal's desire for more did not decrease as the half drew to a close, and the potentially record-breaking goal would fly past Grbic in the 39th minute, as Saka produced a slick turn and touch to lose Osborn and found an unmarked Rice, whose swept a first-time strike into the far corner.
After witnessing his XI become just the second team in top-flight history to score at least five goals in three successive top-flight away games - emulating the Burnley crop of 1961 - Arteta had seen enough from Saka, taking the Englishman off for a well-earned rest as Fabio Vieira made his first appearance since November.
The visitors lacked their first-half urgency after the restart and had a couple of bits of defending to do, but they remained utterly dominant and made the net bulge in front of their fans in the 58th minute, as Havertz took down a long ball with a sublime touch before teeing up White, whose stunning left-footed effort from just inside the box nestled into the bottom corner.
The defender's strike marked the 10,000th goal in Arsenal's competitive history, although Arteta's evening was not entirely perfect, as Martinelli had to be helped off the pitch just after the hour mark and could not put any weight on his right foot as he made way for the returning Gabriel Jesus.
A raft of changes also saw Thomas Partey introduced for his first match in nearly five months, and Jesus almost had Arsenal in seventh heaven with a curling strike in the 82nd minute, but Grbic was alert and produced a strong save with his outstretched right hand.
Now boasting the best goal difference and most goals in the Premier League, Arsenal maintain their two-point disadvantage to Liverpool in third place, while a battered and bruised Sheffield United remain rooted to the foot of the pile, 11 points from safety.
The Gunners are back at home on Saturday evening, hosting Brentford in a London derby, a couple of hours after the Blades - who are now the first team in English football history to concede five goals in four straight home games - face Bournemouth at the Vitality Stadium.