However, the Lions would not win a game until Week 13 against the division rival Minnesota Vikings, ending a 15-game, 364-day winless streak.

The Lions added 49-yard field goal by Austin Seibert, making the score 31–10 in favor of San Francisco at half-time.

In week 2, the Lions visited their divisional rival the Green Bay Packers on Monday Night Football.

The Lions opened the scoring in the first quarter via a five-yard touchdown pass from Jared Goff to Quintez Cephus.

The Lions responded with a 43-yard field goal by Austin Seibert, making the score 17–14 in favor of Detroit at half-time.

The Packers extended their lead in the fourth quarter via a one-yard touchdown run from Jones, making the final score 35–17 in favor of Green Bay.

The Ravens responded with an NFL-record 66-yard field goal by Tucker, making the final score 19–17 in favor of Baltimore.

The Bears scored ten points in the third quarter via a four-yard touchdown run from Damien Williams and a 33-yard field goal by Cairo Santos.

The Vikings added 10 points in the second quarter via a 38-yard field goal by Joseph, and a 15-yard touchdown pass from Kirk Cousins to Alexander Mattison.

The Vikings responded with a 54-yard field goal by Joseph as time expired, making the final score 19–17 in favor of Minnesota.

The Bengals extended their lead in the second quarter via a 38-yard field goal by Evan McPherson, making the score 10–0 in favor of Cincinnati at half-time.

The Bengals added 10 points in the third quarter via a 40-yard touchdown pass from Burrow to Joe Mixon and a 40-yard field goal by McPherson.

The Lions responded with a 41-yard field goal by Seibert, making the score 17–16 in favor of Los Angeles at half-time.

The Rams extended their lead via a 47-yard field goal by Gay, making the final score 28–19 in favor of Los Angeles.

The Eagles added 10 points in the second quarter via a 43-yard field goal by Jake Elliott and a four-yard touchdown run from Jordan Howard, making the score 17–0 in favor of Philadelphia at half-time.

The Steelers opened the scoring in the first quarter via a nine-yard touchdown pass from Mason Rudolph to James Washington.

In the third quarter the Lions took their first lead of the game via a 42-yard touchdown run from Godwin Igwebuike and a missed extra point by Santoso.

The Steelers scored the only points of the fourth quarter via a 51-yard field goal by Boswell to tie the game and force overtime.

For their annual Thanksgiving Day game, the Lions hosted a rematch against their divisional rival the Chicago Bears.

The Lions unsuccessfully attempted to win their first game on Thanksgiving since 2016, as well as end their 14-game non-winning streak dating back to week 13 of the 2020 season, which was also against the Bears.

The Bears responded with a 28-yard field goal by Santos as time expired, making the final score 16–14 in favor of Chicago.

The Vikings scored nine points in the third quarter via a 31-yard field goal by Joseph, and an eight-yard touchdown run from Alexander Mattison.

The Lions scored 10 points in the second quarter via a seven-yard touchdown pass from Jared Goff to Kalif Raymond and a 36-yard field goal by Riley Patterson.

The Broncos responded with a 52-yard field goal by Brandon McManus, which made the score 17–10 in favor of Denver at half-time.

The Falcons took their first lead of the game in the fourth quarter via a 12-yard touchdown pass from Matt Ryan to Hayden Hurst.

The Seahawks scored ten points in the first quarter via a 15-yard touchdown run from Rashaad Penny and a 51-yard field goal by Jason Myers.

The Seahawks extended their lead via two field goals by Myers from 36-yards, and 42-yards, respectively, making the final score 51–29 in favor of Seattle.

The Lions took their first lead of the game in the second quarter via a two-yard touchdown pass from Jared Goff to Amon-Ra St. Brown.

The Packers responded with a 29-yard touchdown pass from Rodgers to Lazard, and a missed extra point by Mason Crosby.

The Packers scored 14 points in the fourth quarter via a one-yard touchdown run from Patrick Taylor and a failed two-point conversion attempt, then a 62-yard touchdown pass from Jordan Love to Josiah Deguara and a two-point conversion run from Love to regain the lead for the first time since the first quarter.