Tammy Abraham fired the Giallorossi ahead early on, before bundling home the first of three goals in four minutes, as Sergio Oliveira and Nicolo Zaniolo put the capital club out of sight.
Empoli fought back after the break and halved the deficit through Andrea Pinamonti and Nedim Bajrami, but could not find the remaining goals to seal a famous comeback.
Rui Patricio 6; Mancini 6, Smalling 5.5, Ibanez 5.5; Karsdorp 6, Cristante 6.5, Sergio Oliveira 7.5, Mkhitaryan 6.5 (’75 Veretout 6), Maitland-Niles 6 (’60 Vina 6); Zaniolo 7 (’79 Afena-Gyan N/A); Abraham 8
Player of the match: Tammy Abraham
The England international set his team on their way to victory with a first half brace, firing in low after controlling a Sergio Oliveira shot and spinning to lose his man, before reacting quickest to turn a corner in. Now into double figures for Serie A goals, the former Chelsea striker has found his form and his role leading the line for Roma.