In the match, Paulo Dybala also returned to action, having been out injured for a month; Lukaku’s perfect penalty ended before the lanky Belgian and Sardar Azmoun turned Lecce things around with two stoppage-time goals.
Roma, with this win, will go into the Rome derby with a high level of confidence.
The hosts made a dramatic start within the opening minute as Dybala’s shot got deflected off Federico Baschirotto’s fingertips, and a penalty was awarded following the VAR on-field review.
Lukaku stepped up but couldn’t convert his penalty for the first time in Italy after 14 consecutive spot-kicks. Wladimiro Falcone’s legs parried his effort and placed in the center of the pole.
Falcone was also called into action, making a full stretch for a one-handed save on the Houssem Aouar right-foot curler that was going into the far bottom corner.
Dybala produced two dangerous volleys in the same move, the first charged down, the second flashing inches wide of the near post.
Nikola Krstovic’s efforts took a deflection from Diego Llorente, and it took the sting out of his effort from 12 yards into the arms of Rui Patricio.
The referee then turned down Lameck Banda’s penalty appeals as Llorente got the slightest touch to the ball.
It became an end-to-end attack after the restart, as Marin Pongracic robbed Aouar and shrugged off three to test Rui Patricio at the near post.
Falcine also saved with his foot when Stephan El Shaarawy laid it off for Lukaku.
After Krstovic broke away through three defenders, Evan Ndicka made the decisive block, while Aouar’s cross-shot skimmed Lukaku’s head, and Gianluca Mancini nodded a Dybala corner wide.
Lecce had a counterattack and finally broke the deadlock. Banda surged down the left and cut back inside Mancini and Llorente before releasing the ball across for Pontus Almqvist to sweep in from 12 yards.
Dybala almost restored parity for the hosts, but his effort went off target after combining with Lukaku.
Lecce almost made it two as Gabriel Strefezza robbed Renato Sanches for an angled drive that scraped a coat of paint off the far post.
Roma were eventually rewarded for their push as they scored the equaliser in stoppages.
Nicola Zalewski flew down the left and released a cross that found the head of Sardar Azmoun for his first goal in the Giallorossi jersey.
Roma completed the turnaround moments later. Dybala surged through the center and threaded through Lukaku, who used his strength to turn one defender before sending another to the ground and firing in the winner from eight yards.