[3] On the final day of the 2016 mid year transfer window, he was released by Fiorentina, and subsequently joined Virtus Entella.

[4] After several months playing for the Entella Primavera side, Zaniolo was given his professional debut in Serie B on 11 March 2017, aged 17, in a 3–2 win against Benevento.

[6] In June 2018, it was reported that Zaniolo and Davide Santon had joined Roma as a part of the deal moving Radja Nainggolan to Inter.

[11][12] Zaniolo completed his medical on 25 June, and signed a five-year contract with the club, for a fee of €4.5 million plus 15% resell revenue.

[13][14] He made his first appearance for Roma and UEFA Champions League debut on 19 September, in a 3–0 defeat to Real Madrid at the Santiago Bernabéu.

[26] Zaniolo missed the entire 2020–21 season due to another anterior cruciate ligament injury sustained in September 2020 over the international break.

[30] On the field, Zaniolo continued his struggle for form, deployed as a right sided hold-up player, playing through thigh and shoulder injuries.

[33] He made an impressive debut with his new club in a friendly against Alanyaspor on 26 February, coming on in the 80th minute and scoring a goal in stoppage time.

Zaniolo admitted to gambling on card games, but strongly denied any involvement in the sports betting that saw Italy teammate Sandro Tonali issued with a lengthy footballing ban.

[45] On 13 May 2024, Zaniolo suffered a broken metatarsal in a 3–3 Premier League draw against Liverpool which ended his season one match prematurely.

[52] He made his debut with the Italy U21 team on 11 October 2018, under manager Luigi Di Biagio, in a 1–0 friendly defeat to Belgium.

[53][54] He made his debut with the senior team on 23 March 2019, entering as a substitute for Verratti in a 2–0 home win over Finland in Italy's opening UEFA Euro 2020 qualifying match.

[55] He made his first start for Italy on 15 October, in a 5–0 away win against Liechtenstein, in a Euro 2020 qualifier[56] (the opposition that day included Yanik Frick, a childhood friend).

[58] On 7 September 2020, after being called up for the start of Italy's campaign in the 2020–21 UEFA Nations League, he suffered a second anterior cruciate ligament injury in eight months, this time in his left knee, in an eventual 1–0 away win over the Netherlands.