The 29-year-old moved to England during the close-season from Feyenoord and has scored four goals in his opening six league games for the club.
That form has convinced Italy coach Antonio Conte to name him in a 26-man squad for Euro 2016 qualifiers against Azerbaijan and Malta.
Pelle has represented Italy at Under-21 and Under-20 level earlier in his career and was previously unable to impress Cesare Prandelli of his abilities, despite 50 league goals in two seasons with Feyenoord.
However, that has all changed after new coach Conte opted to give him a chance, with Empoli defender Daniele Rugani also handed a first call-up.
Liverpool striker Mario Balotelli is again omitted from Conte's squad, though, having not featured in the wins over Netherlands and Norway in early September.
The 24-year-old has only scored once in eight matches for Brendan Rodgers' side in all competitions since his move from Milan and he has yet to break his duck in the league.
However, there are recalls for Milan's Giacomo Bonaventura, Thiago Motta of Paris Saint-Germain and Fiorentina wing-back Manuel Pasqual.
Italy face Azerbaijan in Palermo on Friday before travelling to Malta on October 13.
Squad in full:
Goalkeepers: Gianluigi Buffon (Juventus), Mattia Perin (Genoa), Salvatore Sirigu (PSG)
Defenders: Leonardo Bonucci, Giorgio Chiellini (both Juventus), Matteo Darmian (Torino), Mattia De Sciglio (Milan), Angelo Ogbonna (Juventus), Manuel Pasqual (Fiorentina), Andrea Ranocchia (Inter), Daniele Rugani (Empoli).
Midfielders: Alberto Aquilani (Fiorentina), Giacomo Bonaventura (Milan), Antonio Candreva (Lazio), Alessandro Florenzi (Roma), Claudio Marchisio (Juventus), Thiago Motta (Paris Saint-Germain), Marco Parolo (Lazio), Andrea Poli (Milan), Marco Verratti (Paris Saint-Germain).
Forwards: Mattia Destro (Roma), Sebastian Giovinco (Juventus), Ciro Immobile (Borussia Dortmund), Pablo Daniel Osvaldo (Inter), Graziano Pelle (Southampton), Simone Zaza (Sassuolo).
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