Giampaolo Pazzini and Yuto Nagatomo scored either side of half-time for Claudio Ranieri's injury-plagued team and move them away from the danger zone.
Miroslav Klose scored twice, including the winning goal three minutes from time, to give Lazio a 3-2 win at Lecce where coach Serse Cosmi was making his debut with the hosts.
Genoa won 2-0 at Siena and Romania forward Adrian Mutu gave Cesena a 1-0 win at Palermo, ending the Sicilians' 100 percent home record.
Inter were missing captain Javier Zanetti, suspended following the first red card of his Serie A career in last week's home defeat by Udinese, while Wesley Sneijder, Diego Forlan, Dejan Stankovic and Cristian Chivu were among those on the injury list.
Having also lost 2-1 at home to CSKA Moscow in the Champions League on Tuesday, the pressure was back on Inter who are struggling to recover from a dreadful start to the season under Gian Piero Gasperini's short-lived leadership.
Inter broke through four minutes before the break when Fiorentina were caught out by Coutinho's lobbed pass and Pazzini pounced to cleverly flick the ball past Boruc.
Four minutes after the re-start, there was confusion in the Fiorentina defence as three players tried to clear Pazzini's ball into the area.
Inter's win left them ninth with 17 points, one more than Fiorentina who dropped to 14th.
Albania midfielder Lorik Cana put Lazio in front in the 48th minute, almost immediately after coming on as a half-time substitute, before Stefano Ferrario headed in Luis Muriel's lobbed cross to level just before the hour.
In the 87th minute, Klose got in front of his markers to head in Djibril Cisse's perfectly flighted cross to score his eighth goal of the season.
