After the hosts had dominated the opening half, Dessena grabbed the match-winner shortly after half-time when he dived to head in a floated cross from Thiago Ribeiro.
Sampdoria had a Gianni Munari effort ruled out for offside but their poor run continued - they have now lost four on the spin - to fall out of the top half of the Serie A table.
Samp boss Ciro Ferrara was without a number of his first-choice names with Andrea Costa, Maxi Lopez and Sergio Romero suspended, while injury and illness kept Enzo Maresca and Pedro Obiang sidelined.
Despite their absences the promoted hosts made all the running in the opening 45 minutes.
Marcelo Estigaribbia fired an early warning shot when he blazed over on five minutes before Daniele Gastaldello headed narrowly wide of the left-hand post after Fernando Tissone's cross picked him out.
Sampdoria continued to press forward but Estigaribbia wasted two more chances around the half-hour.
The Paraguay international first blasted well wide after trying his luck from outside the area and then, after a clever pass from Tissone, he was inches away.
Cagliari had offered next to nothing for the majority of the half but almost stole ahead on 43 minutes when Nene shot just wide of the left-hand post.
The visitors did take an unexpected lead two minutes after half-time when they hit Sampdoria on the break.
Ribeiro floated a cross in from the right that Dessena showed greater urgency to get on the end of as he sprinted between two defenders before diving to head in at the near post.
Sampdoria attempted to immediately recover the situation but Gastaldello failed to head on target from Citadin Eder's free-kick, and when they did find the net Munari was on the wrong end of a tight offside decision.
It was the best Sampdoria could muster in the final moments and Dessena could even have grabbed a second but his drilled shot on 84 minutes was punched away by Tommaso Berni.