Substitute Gaston Ramirez put Bologna ahead on the stroke of half-time before Robert Acquafresca made it 2-0 in the 63rd minute as Novara conceded their first defeat at home.
Pioli was appointed before the international break following the sacking of Pierpaolo Bisoli, who led Bologna to just one point in their opening five games.
In the first half, Bologna had the look of a side who were going to suffer a fourth consecutive defeat as Novara dominated.
Carlo Alberto Ludi was first to test Bologna goalkeeper Federico Agliardi with a 30-yard strike which was saved.
Agliardi did even better in the 14th minute as he kept out Takayuki Morimoto's eight-yard shot.
Novara missed a great chance to go in front one minute later.
Massimo Paci got his head on Alex Pinardi's cross and his powerful effort went just wide of the far post.
Ramirez replaced injured Alessandro Diamanti in the 19th minute as Bologna continued to struggle to put a good move together.
The hosts suffered a setback in the 43rd minute when goalkeeper Samir Ujkani got hurt and was forced to leave the pitch, with Alberto Fontana taking his place in goal.
Bologna scored soon after in what was their first chance of the game.
Marco Di Vaio fed Ramirez inside the area and he struck the ball past Fontana.
Di Vaio should have doubled the advantage early in the second half but the Bologna captain saw his close-range effort denied by Fontana.
In the 53rd minute, Novara coach Attilio Tesser was sent to the stands for protesting to the referee.
The visitors extended their lead after the hour mark.
A fast break from Bologna saw Acquafresca surge inside the area before firing past Fontana.
With 20 minutes remaining, Di Vaio could have got on the scoresheet but his close-range effort was kept out by Fontana.
Substitute Henry Gimenez was unlucky not to make it 3-0 with one minute to go with his 12-yard attempt hitting the crossbar.