The win gave the Patriots (7-5) a 4-1 record in a five-game, 25-day November stretch and moved them into sole possession of second place in the AFC East, a half game Miami (7-4) and a half game ahead of the New York Jets (6-5).
Miami plays at Buffalo on Sunday and the Jets visit Oakland on Monday night.
"Big players made big plays for us," said Patriots Coach Bill Belichick said. "I expected pretty much the game we got there. We feel good about coming out on top."
The Lions (3-9) have lost consecutive Thanksgiving Day games for the first time since 1992-93.
Troy Brown was the star on offense for the Patriots, catching 10 passes for 111 yards, but it was the defense which carried New England to its first Thanksgiving Day win in three attempts.
Bruschi made the first big play for the defense when he intercepted a short pass over the middle by Joey Harrington, raced to the left sideline and leaped into the end zone, increasing New England's lead to 10-0 just 5:16 into the game.
"You have to have the right read, then you go back into coverage. If the route comes your way, you have an opportunity for the interception," Bruschi said.
"He (Bruschi) just got me," Harrington said. "I thought he was coming weak side, bluffed for a second and then took off for the other side. He covered, slid back inside and I didn't see him."
Harrington's second interception squelched a scoring opportunity for the Lions after linebacker Chris Claiborne blocked a punt by Ken Walter. Harrington attempted to escape pressure from defensive end Anthony Pleasant when he floated a pass which was picked off by defensive end Willie McGinest picked it off and returned it two yards to the 18.
"He (Harrington) kind of forced it," McGinest said. "I knew it was a screen. He was looking for the back (Stewart). I just ran to the back and with the good hands I have I made the play."
Later in the quarter, Harrington attempted to hit running back James Stewart with a screen pass over the middle, but threw the ball right to defensive end Bobby Hamilton at the Detroit 19.
Two plays later, running back Kevin Faulk turned a short pass by Tom Brady into a 17-yard gain. The Patriots then handed the ball twice to Antowain Smith, who scored on a one-yard run with 2:24 left in the half, increasing New England's lead to 17-3.
Smith finished with 80 yards on 25 carries.
The third overall pick in the draft, Harrington is the seventh different starting quarterback for the Lions over their last 11 Thanksgiving Day games. They hope he is around for many more, although Harrington is experiencing the expected growing pains.
"I can't get discouraged," Harrington said. "I think the experience in the first half turned into a positive for me because I made some adjustments in the second half. I'm learning from all of this stuff."
He was 22 of 44 for 210 yards with the three turnovers in his first holiday affair and has completed just under 50 percent of his passes with 11 touchdowns and 16 interceptions.
"We made the decision to go with Joey and unless something really drastic happens we are going to work through all of his mistakes -- period," said maligned Lions Coach Marty Mornhinweg, who drew criticism for taking the wind instead of the ball in an overtime loss at Chicago last week. "This won't be the last time he throws three interceptions in a game."
Brady, a two-year starter at Michigan in 1998 and 1999, received a warm ovation from the crowd and completed 18 of 30 passes for 210 yards with an interception. He surpassed 3,000 passing yards for the season, but failed to add to his NFL-best total of 24 touchdown passes.
"There was a lot of familiarity for me from my days at Michigan," Brady said. "I sure got a warm welcome out there. It seemed like there were more Michigan than Lions fans."
More than half of Brady's completions and yardage went to Brown, who found seams in the middle of the field throughout the day.
Jason Hanson kicked four field goals to account for Detroit's scoring.
The loss was the fourth in a row for the Lions, who slipped into last place in the NFC North.
The Patriots wore the club's 1985 uniforms with red jerseys and white pants, white helmets featuring the "Pat Patriot" logo with white facemasks, and white socks with red and blue horizontal stripes.
The Lions were adorned in their uniforms from 1934-61 with white pants and silver numerals, plain silver helmets with gray facemasks, blue jerseys and black belts.
The Patriots scored 10 points in a span of 22 seconds early in the first quarter and never had their lead reduced to less than a touchdown. They opened with a 10-play, 62-yard drive which featured a 28-yard pass to David Patten and resulted in a 31-yard field goal by Adam Vinatieri 4:54 into the game.
The day did not start as well for Harrington. After throwing an incompletion on Detroit's first play from scrimmage, Harrington attempted to hit Larry Foster over the middle, but Bruschi diagnosed the play and returned the interception for his second touchdown of the season. The first came on a 48-yard return in a loss at Oakland on Nov. 17.
"He (Bruschi) did a great job of coming across on the slant pattern," Belichick said. "It was a well-executed play on his part."
Harrington engineered a 12-play, 77-yard drive which consumed more than six minutes and resulted in a 23-yard field goal by Hanson with eight seconds left in the first quarter. Rookie receiver Eddie Drummond gained 23 yards on a reverse and Harrington hit Germane Crowell with a 19-yard pass to highlight the drive.
Rookie Deion Branch returned the ensuing kickoff 63 yards to the Detroit 32, where he was tackled from behind by Bracey Walker. However, after two runs by Smith for 13 yards, Brady rolled right and threw an ill-advised pass over the middle that was intercepted by rookie cornerback Chris Cash and returned 11 yards to the 27. It was only Brady's second interception in his last 192 pass attempts.
The Lions also squandered a scoring opportunity in the second quarter when Harrington threw his second interception, four plays after Claiborne's blocked punt.
Hanson's second field goal, a 45-yarder with 30 seconds left in the half, made him the franchise's all-time leading scorer with 1,114 points, surpassing Eddie Murray.
"That was a special one because I've been here kicking field goals for 11 years," Hanson said. "I wish we would have won the game, but I don't want to go anywhere else. I want to stay here and be part of turning this around."
Hanson's third field goal, a 39-yarder with 4:12 left in the third quarter, pulled the Lions within 17-9. Foster caught two passes for 38 yards to highlight the 13-play, 64-yard drive.
The Patriots then put together a 12-play, 64-yard drive which lasted nearly six minutes and resulted in a 29-yard field goal by Vinatieri with 13:17 left in the fourth quarter. Brown made the big play with a 24-yard catch on a 3rd-and-10 play to the Detroit 38.
Hanson kicked a 46-yard field goal with 9:46 left to again pull the Lions within eight points, but they never got the ball back.