Two goals from Roberto Gagliardini, either side of Matteo Politano's strike, and late Joao Mario and Radja Nainggolan goals moved Luciano Spalletti's side back into second place in Serie A as they won a fourth home league match in a row for the first time in 12 months.
Inter's seventh top-flight win in succession came despite the likes of Mauro Icardi, Matias Vecino and Nainggolan starting on the bench, leaving them in good shape to face Barca in a key Champions League match next week.
Gagliardini put Inter ahead after only 14 minutes, pouncing on a loose ball in the box to prod home from six yards, with the goal standing after a quick check from the referee with the VAR crew.
Two minutes later, the home side had their second. Politano reached Joao Mario's pass ahead of his man and fired low past goalkeeper Ionut Radu for his second goal of the season.
Genoa showed a little improvement before the break but Inter put the result beyond question just three minutes after the restart, when Gagliardini blasted in after Radu had reacted brilliantly to deny Ivan Perisic.
Krzysztof Piatek was summoned from the bench and immediately headed straight at Samir Handanovic from a corner, but Inter's lead could have been greater had Joao Mario and Lautaro Martinez showed a little more composure on the break.
Genoa offered little else to threaten a late comeback, as their run without an away win against Inter stretched to 13 league games, and the Nerazzurri made the victory more one-sided with an injury-time flurry: Joao Mario turned into space and drilled past Radu left-footed from the edge of the box, before substitute Nainggolan headed in the Portugal midfielder's cross with the last touch of the game.
2 - @Inter have scored two goals in the opening 20 minutes with two different Italian players in a Serie A game, for their first time since April 1996 (vs Padova, goals scored by Branca and Carbone). Sprint.#InterGenoa— OptaPaolo (@OptaPaolo) November 3, 2018
What does it mean? Inter back into second and ready for Barcelona
However, their performance was controlled and composed throughout, meaning they eased back into second place and three points behind leaders Juventus, having played a game more.
They should also feel reasonably well rested for the visit of Barca on Tuesday in a crunch Champions League encounter.
Gagliardini stakes his claim
This was only Gagliardini's fourth Serie A start of the season, but it was a performance that might play him into Spalletti's plans next week. He took his goals well and was effective with and without the ball in midfield.
Lazovic caught napping at the wrong moment
Darko Lazovic's failure to clear promptly gifted Politano the chance to make it 2-0 to Inter, and it was a goal from which Genoa never recovered. Lazovic also completed just 62 per cent of his attempted passes, the lowest of any of his side's outfield players.
Key Opta Facts
3 - Inter have scored three goals with Italians players in a single Serie A game for the first time since January 2012, against Parma (Thiago Motta, Pazzini and Faraoni). Tricolore. #InterGenoa pic.twitter.com/KWchHLjYdi— OptaPaolo (@OptaPaolo) November 3, 2018
- Inter have won seven games in a row in Serie A for their first time since January 2017.
- Gagliardini has scored his first brace in Serie A at his 69th appearance in the competition.
- Joao Mário has scored and delivered an assist in the same Serie A game for the first time.
- Inter have won their last six home games in Serie A against Genoa, keeping a clean sheet in their last four.
Inter turn their attentions to the visit of Barca on Tuesday, before next Sunday sees them travel to Atalanta in their final match before the next international break.
Genoa's recent tough run, which has included games against Juventus and Milan as well as the Nerazzurri, concludes with a clash with Napoli in a week's time.