Roma, who started the day level on points with Inter, were always going to struggle to maintain their unbeaten record in Serie A after Ludovic Giuly was shown a straight red card for deliberate handball just 28 minutes in.
The summer signing from Barcelona palmed away Zlatan Ibrahimovic's goalbound strike and, to compound his misery, the Sweden striker slotted home the resulting spot-kick to became the leading scorer in Serie A outright with seven goals.
Reigning champions Inter controlled the tempo of the game after going ahead, but an individual error from Maxwell early in the second half gifted Simone Perrotta an equaliser to give Roma hope.
But Roberto Mancini's side restored their advantage only four minutes later courtesy of a Hernan Crespo strike and moments later the game was effectively over as a contest when Julio Cruz scored a third.
And as Roma pushed men forward, long-serving central defender Ivan Cordoba added a fourth to rub salt into the wounds of the home side.