Pescara spoiled the homecoming as Cagliari played their first match in the renovated Is Arenas stadium.
After a tentative opening half Pescara sprung into life with a goal 50 minutes through Christian Terlizzi, who turned home a well-worked free kick.
Any response from Caglari suffered a massive blow just three minutes later, when defender Luke Rossetini was sent off for two bookings after a late challenge.
Former Manchester City and Rangers winger Vladimir Weiss took full advantage to give Pescara a two-goal advantage 15 minutes from time.
Cagliari were given a glimmer of hope in the final stages when Mauricio Pinilla scored a penalty that he had won almost single-handedly.
Pescara held on to pile the pressure on Cagliari coach Massimo Ficcadenti, who has failed to win any of his six matches in charge this season.