The result comes after less than a week from Inter's 3-0 Coppa Italia defeat at the hands of Sampdoria on the same ground.
Swedish striker Zlatan Ibrahimovic and youngster Mario Balotelli scored for Inter to earn Jose Mourinho's win a morale win ahead of the Nerazzuri's clash with Manchester United in the UEFA Champions League.
The game had a very eventful start, as Genoa could have scored on 30 seconds, before Dejan Stankovic's ball broke the home side's offside trap and fell to Ibrahimovic 60 seconds later.
The former Juventus man made no mistakes when he chipped a lovely effort past Rubinho in the Genoa goal.
Thiago Motta almost equalized for Genoa on 20 minutes, but the Brazilian's header was brilliantly saved by Julio Cesar.
Inter's second came when Ibra flicked down a high ball towards Balotelli. The 18-year-old rounded off Rubinho and his weak shot finally made it across the line despite Marco Rossi's late clearance.
Despite the win, Inter were unfortunate to lose centre backs Marco Materazzi and Nicolas Burdisso, who both had to come out injured.
Watch the game's goals