The Abruzzo outfit had two men sent off after Francesco Valiani scored the only goal of the game to condemn promoted Pescara to their eighth defeat of the season.
A statement on pescaracalcio.com read: "At the end of the game, Giovanni Stroppa handed his resignation from his position of head coach at Pescara to president Daniele Sebastiani and director of sport (Daniele) Delli Carri."
Following Stroppa's departure, Delli Carri told Gazzetta.it: "Stroppa has decided to resign and we have accepted his decision.
"We didn't see this decision coming, especially seeing as I said before the game that we would not change the coach even if we lost today [Sunday].
"The responsibility for this defeat lies with both the coaches and the players.
"Now we have to reflect and analyse the situation, but it's too early to name names."
Former Italy midfielder Stroppa replaced veteran coach Zdenek Zeman at the Stadio Adriatico in June as the Czech tactician accepted the role of head coach at Roma.
Zeman had led the Delfini to the Serie B title but Stroppa struggled to replicate last season's form without the services of strikers Lorenzo Insigne and Ciro Immobile, who returned to their respective parent clubs Napoli and Genoa after bountiful loan spells.
Stroppa did manage to deliver back-to-back wins over Palermo and Cagliari in September but that proved to be a false dawn as Pescara went on to earn just one point in October.
Angry fans attempted to breach the changing rooms at the Stadio Adriatico following a goalless draw with Atalanta, with Sebastiani publicly supporting his coach and condemning the actions of the supporters.
But a 2-0 defeat at Chievo prompted Sebastiani to change his mind and issue the 44-year-old with an ultimatum, Stroppa responding by securing victory over Parma and stabilising the club in mid-table.
Sunday's reverse at Siena proved to be the final straw, though, especially as it followed a 6-1 home hammering by reigning Italian champions Juventus, and Pescara find themselves looking for a new manager.
The north-east outfit sit in 17th place, one point clear of Siena and the relegation zone, having earned 11 points from 13 games.