Quagliarella got off the mark in style when he met Bartosz Bereszynski's cross with an acrobatic volley in the fourth minute.
The 36-year-old then struck again for eighth-placed Sampdoria seven minutes later with a towering header from Karol Linetty's cross.
Those goals took his league tally to 19, making him Serie A's joint top scorer alongside Cristiano Ronaldo, of Juventus.
Quagliarella was still not finished as he struck the post with a 30-metre drive before halftime.
SPAL thought they had pulled a goal back on the hour after Sergio Floccari headed in from Jasmin Kurtic's free kick but it was ruled out after a lengthy VAR review, seemingly for offside against Andrea Petagna who was judged to be interfering with play.
Two weeks earlier, SPAL had a goal disallowed and a penalty was awarded to opponents Fiorentina instead after officials spotted an infringement in the SPAL area before they broke upfield.
Kurtic curled in a free kick to pull one back in the fourth minute of stoppage time but SPAL, who are five points above the relegation zone, had defender Thiago Cionek shown a straight red card for denying Gregoire Defrel a clear scoring chance.
