Balotelli returned to Serie A after more than four years in October and has made six appearances totalling just 57 minutes.
The 34-year-old was sent on with seven minutes remaining in Saturday's match against Napoli and almost had an immediate impact as Andrea Pinamonti's glancing header clipped Balotelli's knee but goalkeeper Alex Meret managed to push it off the post.
It was one of several decisive saves by Meret in the second half as Genoa came out fighting after going into the break two goals down following headers from Frank Anguissa and Amir Rrahmani.
Pinamonti got Genoa back into it six minutes into the second half with a fine finish into the bottom right corner but the home side went on to suffer their first defeat since hiring Patrick Vieira as coach last month.
It was also Genoa's first match since coming under the ownership of Romanian businessman Dan Șucu.
The loss left Genoa 13th in Serie A but only two points above the relegation zone.
Napoli moved a point above Atalanta, who host Empoli on Sunday.
Lazio rebounded from a dismal 6-0 thrashing at home to Inter Milan by winning at lowly Lecce 2-1 but it was far from convincing despite Lecce playing the entire second half with 10 men.
Lecce's chances of getting something from the match appeared to evaporate on the stroke of halftime.
Taty Castellanos' first shot was parried brilliantly by Wladimiro Falcone and his follow-up was cleared off the line by the hand of Lecce defender Frédéric Guilbert, who was shown a straight red card.
Castellanos fired the resulting penalty into the bottom left corner.
Tete Morente volleyed Lecce level five minutes after the break and it seemed as if the 10 men were going to hold out for a point but substitute Adam Marusic — who had only just come off the bench — scored the winner three minutes from time.
Lecce almost leveled in stoppages but Mohamed Kaba's header came off the crossbar.
Lazio moved to fourth while Lecce remained two points clear of the drop zone.
Bologna had a penalty saved but won at Torino 2-0.
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