Down three key contributors in Tobias Harris, Jalen Duren, and Caris LeVert, the Pistons came up with a big win against a Cavaliers team that had taken 13 of the prior 14 clashes between the two teams.
Star guard Cunningham added six rebounds, seven assists, two steals, and a blocked shot. But Jenkins stole the show with a monster 21-point second quarter in which he made all seven of his shots - including six three-pointers.
"My teammates were just finding me and I was open," said Jenkins, who is playing on a two-way contract. "I was given space and the key to the game was (if) you've got an open shot, you've got to shoot."
"They packed the paint a lot, so I just stepped into it with confidence and let it slide."
The Pistons outscored the Cavs 47-28 in the period to seize control, erasing an early nine-point deficit to take a 10-point lead into halftime.
The Cavs, led by 30 points from Donovan Mitchell, whittled a 13-point deficit to two with 1:16 remaining and were within two again with 3.8 seconds left, but Jenkins made two free throws to seal it.
Detroit were a perfect 21-for-21 from the free-throw line, Cunningham making 11 and Jenkins five as they pushed their Eastern Conference lead over the New York Knicks to three games.
Pacers' woes continue
Meanwhile, the Indiana Pacers matched a franchise record for futility with their 12th straight defeat, falling 135-127 to the Magic in Orlando.
The Pacers have been a shadow of the team that fell in last season's NBA Finals, with a string of players hit by injuries since star Tyrese Haliburton suffered a torn Achilles tendon in the championship series that will cost him all of this campaign.
Pacers forward Pascal Siakam led all scorers with 34 points, but the Magic - led by 31 points from Desmond Bane - seized control with a 17-0 run in the second quarter and held on in the face of a late Pacers surge.
The Pacers have now dropped 12 straight for the fourth time in franchise history and the first time since 1989.