England led 17-10 at half-time but pulled away after the pause to register their 24th win over Italy who have lost 13 consecutive games in the championship.
"It was very positive," England coach Eddie Jones told ITV. "We knew that they were going to hang in there, but we ran away with it in the end.
"Sam Simmonds came into his own when the game opened up. He has so much gas. He does his speed work with the backs."
There were mixed emotions for Italy coach Conor O'Shea after a promising display again ended in a thumping Italy defeat. "We played some excellent rugby and contributed to an entertaining game, but I'm proud and annoyed," he said.
"We know we're off in certain areas and the progress we need to make. But we're making it," the former Ireland full-back added.
Owen Farrell, George Ford and Jack Nowell were the other England try scorers while Tommaso Benvenuti and Mattia Bellini touched down for the hosts. Tomasso Allen added five points with a conversion and a penalty.
England are aiming for an unprecedented third consecutive Six Nations crown. On 10 February at Twickenham, they take on Wales who destroyed Scotland 34-7 on Saturday.