Sassuolo participated in Serie A from the 2013–14 season until their relegation in the 2023–24 season, joining a select group of teams to have played in Serie A without belonging to a provincial capital city, such as Savoia (Torre Annunziata), Empoli, Legnano, Pro Patria (Busto Arsizio), Carpi, and Casale.

With Gian Marco Remondina as head coach, they narrowly missed it in 2007, as they lost immediate promotion to Grosseto in the final days of the season, finishing in second-place; and then were defeated by fifth-placed Monza in the play-off semi-finals.

[8] The team's second match was their first at home, against Livorno, where striker Simone Zaza scored Sassuolo's first top-flight goal as they lost 4–1.

[11] On 20 October 2013, Sassuolo won their first Serie A game, defeating Bologna 2–1 at home with goals from Domenico Berardi and Antonio Floro Flores, moving the club off bottom place.

[15] Towards the end of January 2014, Sassuolo were in bottom place and so manager Di Francesco was relieved of his duties and Alberto Malesani was brought in.

The managerial change did not have the desired effects and so in early March, Sassuolo re-entrusted the side to the management of Di Francesco.

[19] On 25 August 2016, Sassuolo qualified for the Europa League group stage after beating Red Star Belgrade 4–1 on aggregate in the playoff round.

[citation needed] On 13 June 2018, Roberto De Zerbi was appointed as manager, after impressing with his possession-based tactics at relegated Benevento in the previous season.

A primary reason for Sassuolo's growth was due to De Zerbi's innovative, attack-minded style of play, which began to flourish and led to a record-breaking Serie A goal return of 69, the most prolific the club has been since promotion in 2013.

After eight matches, Sassuolo was placed second in the table, which in part was the result of the excellent form of the likes of Berardi, Manuel Locatelli, Filip Đuričić, amongst others.

[24] Although the club's form declined slightly in the mid-stage of the season, a 2–0 victory over Lazio on the final matchday meant that Sassuolo reached the same points total as Roma in 7th place, but narrowly missed out on European qualification on goal difference.

[26] De Zerbi announced he would leave the club at the end of the season to take up the vacant head coach position at Shakhtar Donetsk.

[27] On 11 July 2021, Sassuolo's Manuel Locatelli, Domenico Berardi and Giacomo Raspadori were part of the Italy national squad that defeated England in the UEFA Euro 2020 final.

[33] Sassuolo's famous green and black kit originates from a donation from English side Lancaster Rovers FC.