Thuram redirected a cross from Federico Dimarco from close range in the 81st minute on Sunday to finally break through Jose Mourinho's massed defence.
With Mourinho suspended from the dugout and watching from the stands, Roma sat back and absorbed attack after attack from high-flying Inter.
In the first half, Roma conceded 12 shots without a single effort of their own. By the end, Inter had produced 19 shots to the visitors' three.
The win took Simone Inzaghi's side two points clear of Juventus at the top of the table, while Roma stayed eighth.
AC Milan remained third, three points back, after squandering a two-goal advantage in a 2-2 draw at defending champions Napoli.
While the build-up was all about Roma's Lukaku facing his former club, the striker's biggest impact was clearing away Inter corners - giving fans little chance to jeer a player who left acrimoniously after last season and then joined a fierce rival.
Napoli stormed back with goals from Matteo Politano and Giacomo Raspadori early in the second half against Milan after Olivier Giroud had scored twice for the visitors.
Having started without in-form, but injured, centre forward Victor Osimhen, fourth-placed Napoli finished with 10 men after defender Natan picked up a second yellow card in the 89th minute.
Claudio Ranieri's Cagliari became the first team in Serie A history to overturn a three-goal deficit after 70 minutes, coming all the way back to beat visiting Frosinone 4-3 with a double from Leonardo Pavoletti in stoppage time.
Modena and Udinese drew 1-1 with Andrea Colpani and Lorenzo Lucca trading goals.
