Hull's new £3 million striker Dame N'Doye, 29, netted his first goal to mark his debut, while a struggling Aston Villa side slipped into the relegation zone and got their manager Paul Lambert sacked.
Former Croatian international Nikica Jelavic, 29, opened the scoring in the 22nd minute after his shot was deflected from a through ball by transfer deadline day signing N'Doye. This was Jelavic's seventh goal of the season in all competitions.
Hull, who had only won twice in the league before this game, gained in confidence from the opening goal, and the Senegalese striker should have made it 2-0 when he headed wide from El-Mohamady's clipped ball.
N'Doye looked lively on his debut following his transfer from Lokomotiv Moscow, despite Aston Villa having the lion's share of early possession in the first-half. He eventually made it 2-0 with 16 minutes to go in the second half with a close range finish.
Hull could have added to their tally in second-half stoppage time, when Abel Hernandez, 24, shot from 20 yards, when passing to another team-mate looked like the better option.
The closest the Villains came to ending their goal-drought was when Hull keeper McGregor pushed away Ashley Westwood's 25 yard drive and kept out Belgian international striker Christian Benteke's rebound out.
The win was vital for Steve Bruce's men as it took the Tigers to 15th place in the league and gave them some breathing space from the relegation zone, whilst Aston Villa slipped to 18th, and are now looking increasingly worried as they occupy the dreaded third from bottom spot.
The Villains are on a barren run of 10 matches without a win, and they have not scored an away goal in the Premier League in over 8 and a half hours.
During the match some of Villa supporters turned on their manager Paul Lambert, unfolding a "Lambert Out" banner at half-time and calling for his resignation. Lambert joined Villa in 2012 and they finished 15th in the previous two seasons. After the match on Tuesday he was convinced that he would stay and lead Villa to safety, despite the clubs downfall. But on Wednesday, 24 hours after the defeat, Paul Lambert was sacked.