The Hungarians, looking to avoid a sixth straight defeat in Group I, finally picked up their first points thanks to Peter Kabat's second-half double.
The victory also doubled the number of goals Debrecen had scored in the group.
Both sides were already eliminated from the competition, having won a combined one game in 10 matches, and the lack of anything to play for was painfully evident in the desperate first half.
Debrecen posed the greater threat throughout, and only Samp goalkeeper Junior Costa kept the score down.
Kabat's drilled effort from 25 yards was parried by Costa before the goalkeeper held Peter Czvitkovics' shot from closer in.
Czvitkovics then volleyed over the top as half-time approached.
Debrecen stepped up the pressure after the break and Kabat made the breakthrough in the 48th minute.
His first effort from Ondoa Yannick's cross was blocked by defender Daniele Messina, but the former Hungary striker pounced on the rebound and slotted the ball low into the net.
The hosts almost made it 2-0 in the 55th minute as Dejan Simac met Kabat's corner only to see his header parried away by Costa.
Peter Szakaly headed wide as Debrecen continued to push for a second goal and then saw his shot from outside the area tipped round the post by Costa, who was preventing the night from becoming embarrassing for Samp.
Szakaly then fired over the bar before Adam Bodi shot straight at Costa.
The hosts got the second goal their pressure deserved in the 86th minute as Jonathan Rossini's clearance fell to Kabat in the area. The striker mis-hit his shot but the ball still found the bottom corner.
The visitors finally offered something going forward in stoppage time when Massimo Volta's shot was blocked by Dejan Simac, but their performance did not merit a consolation.
Debrecen 2-0 Sampdoria: Match Report - view commentary, squad, and statictics of the game as it happened.
Source: DSG
