Gresini had agonised over whether to race at Valencia at all in the wake of Simoncelli's death.
Its riders Pirro and Yuki Takahashi then timed their qualifying runs perfectly to take a poignant first and second on the Moto2 grid before rain fell yesterday.
In treacherous, drizzly conditions today, Takahashi took an early lead in a battle with Technomag-CIP's Dominique Aegerter, while Pirro initially fell to fifth.
The Italian worked his way back through to second by the time Takahashi had a huge crash at Turn 6 on the sixth lap. He was declared okay at the circuit's medical centre, but taken to hospital for precautionary checks.
Pirro led to the finish thereafter, with team boss Fausto Gresini in floods of tears on the pit wall as his rider crossed the line to claim his maiden Moto2 victory.
Mika Kallio (Marc VDS) ended a tough season on a high by beating Aegerter to second, after long-time second-place man Yonny Hernandez ran off the road late on and fell to sixth. That meant he finished the race in the middle of a huge dice won by MZ's Anthony West, with Kenny Noyes fifth, and Mike di Meglio and Xavier Simeon coming home right behind Hernandez.
Champion Stefan Bradl was one of many riders to crash in the tricky conditions, falling on lap four. Scott Redding and Bradley Smith were among those who did likewise.