Eusebio Di Francesco's side maintained their bid for a top-four finish in Serie A - which would secure their place in next season's Champions League - by beating relegation-threatened SPAL away from home.
Di Francesco rested first-team regulars such as Daniele De Rossi, Edin Dzeko and Alessandro Florenzi with their trip to Liverpool in mind, but Roma were comfortable at Stadio Paolo Mazza.
An own goal by Francesco Vicari put the visitors ahead before half-time, before a quickfire strikes from Radja Nainggolan and Patrik Schick early in the second period sealed the three points.
Roma, therefore, head to Anfield on the back of a four-game unbeaten run in all competitions.