Tyler Morton, Jaden Philogene and Scott Twine scored within the first 20 minutes to put the game out of reach of the managerless visitors.
Philogene added another soon after the restart against a brittle Rotherham side who remain in deep relegation trouble
Hull were ruthless, and perhaps a touch fortunate at times in the build-up to their goals, but the Millers were blown away in the first half and have still claimed just one away point all season.
And though Grant Hall headed home a consolation, Rotherham must now reflect upon the worrying statistic of having conceded 11 goals in their last three games on their travels.
Clearly sensing an opportunity against jaded opponents, Hull ripped out of the traps and opened the scoring after five minutes.
Hall's feeble back-pass put goalkeeper Viktor Johansson in an awful position, from which he did well to stop Liam Delap's initial shot but the ball fell kindly to Morton, who could not miss.
Rotherham were visibly leggy following their hard-earned draw at home to Leeds on Friday and were further punished on nine minutes.
Dexter Lembikisa made an awful mess of Jason Lokilo's back-post cross, with the ball striking the defender's backside and bouncing towards Philogene on the left angle of the six-yard box.
The former Aston Villa playmaker had his back to goal but showed stunning craft with a backheel into the bottom right corner.
Away fans might have been forgiven for thinking that things could not have got any bleaker before the interval.
They were wrong, as Twine added a third after 20 minutes.
Alfie Jones' hopeful loft from deep was hardly threatening, but Hakeem Odoffin recklessly went to ground to gift Morton another chance on goal.
The excellent Liverpool loan signing had the wherewithal to square to Delap, whose fierce strike was saved by Johansson. The ball was tricking towards the goal line but Twine provided the insurance from a yard out for his first City goal.
Caretaker manager Wayne Carlisle's half-time debrief would have been even more painful had Hull centre-back Jacob Greaves shown greater composure in a one-on-one situation with Johansson after 40 minutes.
But whatever Carlisle said at the break made not a jot of difference as Philogene scored a second after 48 minutes.
Twine's initial attempt from Jean Michael Seri's cute ball was again saved by Johansson, but Philogene snaffled up the rebound from close range.
Hall at least reduced the deficit from a 59th-minute corner following smart interplay between Ollie Rathbone and Arvin Appiah.
But that was as good as it got for Rotherham, who look in desperate need of swift managerial guidance on this evidence.