Matri's first half strike dealt a crushing blow to Inter's title hopes.
Juventus kept alive their hopes of snatching a Champions League berth for next season after they beat Inter 1-0 at home on Sunday.
Alessandro Matri scored the only goal in the 30th minute of the Derby d'Italia in which both sides had created several scoring chances.
Inter striker Samuel Eto'o squandered a late chance to equalize when he smashed the ball against the bar despite having an open goal at his mercy.
Inter are now eight points behind AC Milan with a game in hand. Juventus are a further three points behind.
Lazio remain in contention for the Scudetto after winning 2-0 away to Brescia on Sunday.
Edy Reja's team remain seven points off league leaders AC Milan, who thrashed Parma 4-0 on Saturday, and are well in the championship mix.
Goals from Alvaro Gonzalez on 18 minutes and Libor Kozak just before the hour mark ensure Lazio maintained their grip on a Champions Legaue place.
Udinese are not letting up in their pursuit of a top four finish as they cruised to a 3-0 win at troubled Cesena.
Antonio Di Natale scored another brace, either side of a strike by Gokhan Inler, keeping fifth placed Udinese just two points behind third-placed Lazio.
It wasn't such happy news for Palermo whose hopes of securing a Champions League finish suffered a blow as they fell to a shock 4-2 defeat at home to Fiorentina.
The hosts twice took the lead through Javier Pastore and Antonio Nocerino but goals from Alberto Gilardino, Michele Camporese, a Cesare Bovo own goal and captain Riccardo Montolivo turned the game around.
It leaves Palermo just outside the top four having also played a game more than their rivals.
Juventus have now emerged as serious contenders for a Champions League's berth after taking three precious points from Inter.
Midfielder Alberto Aquilani had the first chance of the game, but chipped just over the crossbar.
Juventus winger Milos Krasic started the build-up for the goal, pulling the ball back for Frederik Sorensen to find Matri, who headed his cross past goalkeeper Julio Cesar.
Inter immediately went on the attack, but Esteban Cambiasso hooked his shot over the bar.
Early in the second half, Inter had their best chance, but goalkeeper Gianluigi Buffon punched Giampaolo Pazzini's header away.
Matri had a chance to add a second, but headed Krasic's cross wide from close range. He then took too long when Aquilani played him in and Maicon came back to clear.
Buffon had to rush off his line twice to stop Eto'o, before Matri then fired a shot wide from close range.
With two minutes remaining, Eto'o missed an open goal. He hit the bar from close range after Juventus' defense had failed to cut out Maicon's low cross.
