Borja Mayoral got his first Serie A goal just before the half-hour mark, with Mkhitaryan adding two more before the break to bring his tally to five goals in two games after scoring a hat-trick last time out against Genoa.
Meanwhile, Sassuolo continued its impressive run thanks to goals in either half from Jeremie Boga and Domenico Berardi.
The side from Emilia Romagna is unbeaten this season and is the top scorers with 20 goals in eight games.
In Tuscany, Cesare Prandelli had a nightmare start as coach of struggling Fiorentina with a 1-0 home defeat by promoted Benevento.
Former Italy coach Prandelli returned to the 'Viola' a decade after leaving for the Azzurri job in 2010, after Giuseppe Iachini was sacked, but the team fell to their fourth defeat in eight games.
To add to Prandelli's woes, French midfielder Franck Ribery went off injured just before half-time with Italian international Giacomo Bonaventura pulling up during the warm-up.
"What worries me most is the fragility," said Prandelli.
"At the first difficulty the team lost tactically, technically and personality.
"Perhaps the team succumbed to their fears and negative thoughts when Franck came off."
Riccardo Improta scored his first Serie A goal for Benevento on 52 minutes, slotting in a Gabriele Moncini cross after a Cristiano Biraghi defensive error.
Fiorentina, without a win in three games, slip to 15th in the Serie A table, just behind Benevento, which moves into 14th after ending their four-match losing streak.