With rivals AC Milan not in action until Sunday against Lazio, Inter took full advantage to move to the Serie A summit after beating a Roma side who had gone 12 games unbeaten in the Italian top flight before their trip to the San Siro.
Flying full-back Denzel Dumfries fired his side into the lead on the half-hour mark, before a fine solo effort from Marcelo Brozovic double the dominant hosts' advantage five minutes before the break.
Argentine striker Lautaro Martinez headed home from a corner in the 52nd minute to make it three for Inter.
Henrikh Mkhitaryan fired home in the 85th minute but it was too little too late for the visitors. Inter's fourth successive league win moved them on to 72 points from 33 matches, one ahead of Milan. Roma stay fifth on 58 points.