The Bears took the lead on the nine-play, 90-yard drive in which Trubisky converted a pair of third downs with 35- and 32-yard passes Anthony Miller.
"He made special throws at special times," coach Matt Nagy said.
Chicago sealed the victory on the ensuing possession with Eddie Jackson's interception.
Rookie quarterback David Blough led Detroit's last drive to the Chicago 26 in the final minute before losing 13 yards on a sack to leave a desperation pass as the only option and Jackson picked off his heave.
The Bears (6-6) have won three of four games after losing four in a row, keeping their postseason hopes alive.
"We put ourselves in a good position to have another big game next week," Trubisky said.
The Lions (3-8-1) have lost five straight for the first time under second-year coach Matt Patricia.
"It's one of the toughest teams I've probably ever been around," said Patricia, a former assistant coach with the New England Patriots. "This team fights like probably no other team I've ever seen.
"We've got to find a way to win."
Detroit led for much of the game despite starting a quarterback it acquired from Cleveland for a swap of seventh-round picks after training camp.
"Watch that team fight and rally behind somebody like that, I think you can tell how much all those men in that room care about each other," Patricia said.
Blough, an undrafted player from Purdue, threw a 75-yard TD on his first completion to Kenny Golladay to pull the Lions into a 7-all tie. Blough threw an 8-yard TD pass to Marvin Jones late in the first quarter to put Detroit ahead 14-7.
Trubisky had an 18-yard TD pass to rookie tight end Jesper Horsted to make it 17-all late in the third quarter.
Trubisky finished 29 of 38 with three TDs, matching a season high he also equaled in a win over Detroit earlier this month, for 338 yards and an interception. He got off to a strong start with a 10-yard pass to Allen Robinson and closed the game well enough for Chicago to score more than 20 points for the first time in more than a month.
Blough was 22 of 38 for 280 yards with two TDs and an interception.
"This is what you dream about as a kid," Blough said. "I'm thankful for it all, all the ups and downs."
"Probably one of the biggest plays in the game," Nagy said. "To make a shoestring tackle was an absolute game-changer."
Patricia choose to kick a 24-yard field goal for a 20-17 lead with 10:47 left instead of going for it on fourth-and-1 from the Bears 5.
Chicago had 10 penalties for 89 yards and Detroit was flagged nine times for 85 yards.
"If there's a negative to the game, the improvement we need to make is with penalties," Nagy said.
SHOW GOES ON
Brothers Osborne, a country music duo, performed at halftime and the show did not go as planned. Fans were asked to turn on the flashlights on their mobile phones when the lights were turned off at Ford Field. After the lights dimmed, the indoor stadium was illuminated again before going dark following an awkward delay.
The technical difficulties led to the musical artists being on the field longer than expected, forcing players to warm up behind and around an elaborate stage.
Ford Field officials said in a statement that "parts of the stadium lost power due to an outside utility failure. Though it was quickly restored, the sound system transmitter required two minutes to reset and reconnect."
Bears: CB Prince Amukamara went down and walked off the field slowly late in the game after breaking up a pass. Four starters WR Taylor Gabriel (concussion), TE Adam Shaheen (foot), OT Bobby Massie (ankle) and LB Danny Trevathan (elbow) were inactive.
Bears: Host Dallas on Thursday, Dec. 5.
Lions: Play at Minnesota on Dec. 8.
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