The Denmark international pounced from close range with 56 minutes gone to fire the home side ahead after strike-partner Fraizer Campbell's shot had twice hit the woodwork with the Spaniard unable to do anything about it.
Reina was the goalkeeper beaten by Darren Bent's infamous beachball goal at the Stadium of Light, and could be forgiven for not counting the venue among his favourites in England.
Bendtner's strike ended the Black Cats' three-game winless Premier League run and in the process dealt a further blow to the Reds' hopes of dragging themselves into a Champions League spot - they trail sixth-placed Newcastle by five points with 11 games remaining.
After all the drama of last weekend's derby trip to St James' Park, it was perhaps inevitable that the game would not live up to one which has occupied the minds of the Wearside faithful ever since.
In the event, the opening 45 minutes was tepid by comparison, and although there was no lack of effort or endeavour, neither side was able to create clear-cut opportunities.
Encouraged by an uncertain display by Liverpool central defender Sebastian Coates, Bendtner - whose penalty almost claimed the derby headlines, caused problems throughout the first half - although was never really able to test Reina.
At the other end, Newcastle old boy Crag Bellamy and striker Luis Suarez were lively, but again, Simon Mignolet's anxious moments were few and far between.
It was Black Cats defender John O'Shea, playing with a lightweight cast protecting a broken bone in his hand, who almost opened the scoring with nine minutes gone when he glanced a header just high and wide from Sebastian Larsson's free-kick.
Bendtner failed to trouble Reina unduly two minutes later after Campbell had headed down Larsson's corner to him, and the Dane saw his low cross elude all the red and white shirts in the middle seconds later.
But as the half wore on, the visitors started to make to make an impression, and Wayne Bridge - making his first start for Sunderland - managed to do just enough to put off Suarez as he stooped to meet Charlie Adam's corner just two yards out.
Adam himself blazed a 32nd-minute high over after running on the ball on the edge of the penalty area seconds after Dirk Kuyt had seen a flicked header easily saved by Mignolet.
Craig Gardner failed to hit the target from distance six minutes before the break after being set up neatly by Bendtner, but it was Mignolet who proved the busier of the two keepers as the half drew to a close.
The Belgium international almost misjudged Adam's 43rd-minute free-kick, but eventually managed to tip it over the bar at full-stretch, and he produced a vital block after Suarez got in and shot from a tight angle in injury time.
Sunderland returned in determined mood and went close with 50 minutes gone when in his eagerness to get to James McClean's driven cross ahead of Campbell, Martin Skrtel only succeeded in prompting his own keeper to make a smart save.
The home side took the lead in bizarre fashion, after Campbell picked up possession 25 yards out and cut inside Skrtel before sending a skidding shot towards goal.
The England international was unfortunate to see his effort come back off the foot of the post after beating Reina, but the ball hit the keeper on the back and bounced on to the woodwork for a second time to allow Bendtner to fire home from close range.
Liverpool's response saw Adam shoot wide from 20 yards with 65 minutes gone, and as the travelling fans starting to plead with manager Kenny Dalglish to introduce Steven Gerrard from the bench, the Scot obliged as he and Andy Carroll replaced Bellamy and Adam with 21 minutes remaining.
The pair combined to good effect within two minutes when Carroll headed down for Gerrard, but the midfielder's shot was claimed easily by Mignolet.
For all the visitors' efforts, Sunderland managed to negotiate the final few minutes with few scares, although the sight of Bendtner leaving the field on a stretcher after a clash with Skrtel would have tempered manager Martin O'Neill's joy.