In week 5, the Lions hosted the Philadelphia Eagles to start a three-game home stand. The Lions took a 14-0 lead in the first quarter with a pair of touchdown catches by Theo Riddick, from one and 17 yards out respectively. The Eagles responded in the second quarter with a one-yard touchdown pass from Carson Wentz to Ryan Mathews, cutting the Lions lead to seven points. The Lions added to their lead with a one-yard touchdown pass from Stafford to Marvin Jones. The Eagles responded with a 50-yard field goal from Caleb Sturgis, which made the score 21-10 in favor of the Lions at halftime. The Eagles scored 10 points in the third quarter via a one-yard touchdown pass from Wentz to Josh Huff, and a 33-yard field goal from Sturgis, cutting the Lions lead to one point. The Eagles took their first lead of the game, going up 23-21 in the fourth quarter on a 49-yard field goal from Sturgis. At the 2:34 mark of the final quarter, Darius Slay forced a Ryan Mathews fumble, which the Lions recovered inside Eagles territory. This was Philadelphia's first turnover of the 2016 season. The Lions got into range for a 29-yard Matt Prater field goal, making the score 24-23 with 1:28 left. Darius Slay intercepted a Wentz pass on the Eagles' next play from scrimmage, sealing the Lions victory and giving the Eagles their first loss of the season.

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