The score was tied by halftime on Monday (Tuesday AEDT) and again in the 65th minute thanks to Armand Laurienté's second goal for host Sassuolo.
Mastantuono, playing his first Serie A campaign after arriving from Real Madrid, got the decisive goal in the 79th. Teenage midfielder Víctor Valdepenas sealed the win in stoppage time.
Fiorentina, on their second coach of the season, had not tasted victory since September 11. The Tuscan side have risen to 16th in the 20-team top flight.
Sassuolo suffered a fourth consecutive defeat and sat 17th on goal difference.
Parma snapped a three-match winless streak by thrashing Atalanta 3-0 in a clash between teams facing relegation concerns.
Parma climbed to 15th place, pushing Fiorentina down in the standings.
Atalanta extended their winless run to four matches.
In La Liga, Bil Nsongo scored in the final minutes to cap Deportivo La Coruna's 2-1 comeback win at home against Osasuna and end a six-game winless streak in the league.
Nsongo, who played a key role in the team's promotion in May, netted in the 87th.
Deportivo last won in the league on September 6. Despite the poor run, they have moved into eighth place.
Osasuna have only one win in their past five matches.
In France, second-half goals from Ludovic Ajorque and Noah Edjouma helped Brest secure a 2-0 victory over Lorient in the ninth round of Ligue 1.
Brest were 10th in the standings, ahead of Lorient on goal difference.
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