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|Brescia's Mario Balotelli played for Inter Milan between 2007-2010 but could not stop his former side from going top of Serie A. (AFP/Miguel MEDINA)|
Lautaro Martinez and Romelu Lukaku scored either side of half-time as Antonio Conte's team climbed above champions Juventus.
An own goal from Milan Skriniar on 76 minutes gave Brescia hope but the home side remain in 18th place and are without a victory since Sep 21.
Conte made two changes from the side which drew 2-2 with Parma on Saturday as Dutch international Stefan de Vrij started in the heart of defence.
Eugenio Corini, under mounting pressure as Brescia boss after a bumpy run, brought in four new faces after the weekend defeat at Genoa and included Alfredo Donnarumma up front to partner Balotelli while handing 31-year-old goalkeeper Enrico Alfonso a Serie A debut.
The visitors claimed an undeserved lead after 23 minutes as De Vrij won a midfield header against Balotelli.
De Vrij's clearance fell to Martinez outside the Brescia box and his deflected shot hit the left foot of defender Andrea Cistana and lobbed Alfonso.
Three minutes into the second half Balotelli threatened Inter's lead but captain Samir Handanovic was equal to his low drive from outside the area.
Despite Brescia's constant pressure since the break Inter doubled their lead after 63 minutes as Lukaku scored his seventh goal in 10 games this season.
The Belgium forward, who joined the Italian club from Manchester United in August, picked up the ball on the right flank and charged forward before curling a shot past Alfonso with his left foot.
Balotelli was denied a chance to halve his former side's lead with less than 20 minutes to go as he skied a rebound over the crossbar after Handanovic saved his point-blank header.
Brescia's hopes of denying Inter top spot were boosted with 14 minutes to play.
Dimitri Bisoli was at the end of a tidy one-two with Donnarumma and his shot flicked off Skriniar to make it 2-1 despite Handanovic's best efforts.
Substitute Alessandro Matri should have claimed a point for Brescia during additional time but he failed to control a cross cleanly at the back post.
Earlier on Tuesday, Darko Lazovic's 10th-minute thunderbolt claimed just a third success of the campaign for Verona as they beat Parma 1-0.
Juve can return top on Wednesday with three points over Genoa, who are reinvigorated under new boss Thiago Motta.