The Italian manager had prioritised this game in midweek, having rested the likes of Gonzalo Higuain and Eden Hazard in the 2-1 win over Malmo. But the changes were too little effect, with opposing manager Ole Gunnar Solskjaer's team selection proving the more effective.
The Norwegian opted for an unfamiliar shape, playing Marcus Rashford and Romelu Lukaku together up front, with Juan Mata playing just ahead of a central midfield trio. It was a formation notably lacking in wingers - but this didn't hinder the Red Devils.
They were fastest out the blocks, with Lukaku almost putting the ball on a plate for Rashford within 90 seconds, only for David Luiz to intercept at the last moment. The chances continued to flow, with Luiz goes close himself with a dipping free-kick minutes later, before Ander Herrera saw a fizzing long-shot saved by Chelsea goalkeeper Kepa.
United made the breakthrough on the half-hour mark, with Paul Pogba picking the ball up on the left wing and, using Juan Mata's overlapping run as a decoy, moved the ball onto his right-foot. The Frenchman then swung in a fine cross to the back post, where Ander Herrera gleefully headed home.
Sarri's men responded well, putting United on the back foot for the next 15 minutes and creating a couple of chances in the process. Gonzalo Higuain was getting into promising positions only to be prevented by last-second tackles or blocks, and a Chelsea equaliser seemed on the cards.
But just before the break, and against the run of play, United hit Chelsea with a sucker punch. Pogba released Rashford on the right, and the young striker waited for men to arrive in the penalty area. He then completed his one-two with Pogba, firing in a cross towards the penalty spot which the Frenchman dived to head into the top corner.
Perhaps thankfully for United, the second period lacked the intensity of the first. Higuain and Hazard both spurned half-chances early in the half, and Nemanja Matic, who had been booked early on, was lucky not to be sent off for a second yellow after quick-fire fouls on Hazard. Chelsea were indignant, referee Kevin Friend was unmoved.
The United fans then began to serenade Sarri with renditions of 'you're getting sacked in the morning', to which the Chelsea fans cruelly joined in. Both sets of supporters then came together to chant, 'bring back Mourinho'. The United fans were being sarcastic, but as for the home fans - who knows?
Alexis Sanchez came on late in the game but struggled to make an impact, while Sarri's last change was an exchange of right-backs - an action that prompted boos from the home fans. Olivier Giroud and Callum Hudson-Odoi remained on the bench, unused. Chelsea struggled to create anything in the final stages of the game, and United held firm to secure a clinical 2-0 victory.
The final whistle brought relief for Ole Gunnar Solskjaer, who had seen his unbeaten streak as interim manager come to an end with defeat against PSG six days earlier, while Maurizio Sarri is now under more scrutiny than ever.