On Friday, September 20, 1935, the Lions opened their season with a 35–0 victory over the Philadelphia Eagles before a crowd of approximately 10,000 at University of Detroit Stadium. Halfback Ernie Caddel scored three touchdowns. Dutch Clark also scored a touchdown, and a fifth came on a 10-yard pass from Pug Vaughan to Frank Christensen. Clark kicked four extra points, and Glenn Presnell kicked the fifth. The Lions prevented the Eagles from making a first down. The Lions totaled 381 total yards against the Eagles, including 324 rushing yards on 57 carries for an average of 6.8 yards per carry. Following the game, the Associated Press reported that the Lions has "definitely established themselves as serious contenders for the 1935 National Professional football league championship."
On September 29, 1935, in the second game of the season, the Lions and Chicago Cardinals played to a 10–10 tie in front of approximately 10,000 spectators at the University of Detroit Stadium. The Lions trailed 3-0 at halftime but scored a touchdown in the third quarter on a 15-yard pass from Dutch Clark to John Schneller. Chicago retook the lead with a touchdown early in the fourth quarter. The Lions then tied the score in the final minutes, as Glenn Presnell kicked a field goal.
In week four, the Lions defeated the Boston Redskins 17–7 in front at Fenway Park in Boston. The Lions opened the scoring in the first quarter with a 35-yard field goal by Glenn Presnell. The Lions added a touchdown in the third quarter on a 20-yard touchdown pass from Ace Gutowsky to Dutch Clark. Both teams scored touchdowns in the fourth quarter. The Lions' final touchdown was fueled by a 40-yard run by Ernie Caddel and a final 10-yard touchdown run by Caddel.
In week five, the Lions suffered their second loss of the season, falling to the Green Bay Packers 13–9 at State Fair Park in Milwaukee. Former Oregon State tackle Tar Schwammel kicked two field goals for the Packers.
Through the first five games, Ernie Caddel was tied with Dale Burnett for the NFL scoring lead with five touchdowns and 30 points. Caddel had gained 297 yards on 39 carries for an average of 7.6 yards per carry.
In the sixth game of the season, the Lions defeated the Boston Redskins 14–0 in front of 14,000 spectators in Detroit. In the first quarter, Ernie Caddel threw a 40-yard touchdown pass to Schneller for the first points of the game. The second half was played in heavy fog, "at times almost completely blotting out all action, and making necessary the use of a white ball." The Redskins drove to the Lions' nine-yard line in the third quarter, but the Lions intercepted a pass to stop the drive. The Lions scored in the fourth quarter on a one-yard plunge by Ace Gutowsky.
In week seven, the Lions narrowly defeated the Chicago Cardinals in the rain and mud at Wrigley Field. The final score was 7–6 with the difference being a successful extra point kicked by Dutch Clark after a 12-yard touchdown run by Ernie Caddel in the first quarter. The Cardinals scored a touchdown in the second quarter but missed the extra point attempt.
Referee: Kahn, Chicago (referee); Elliot, Notre Dame (umpire); Ritter, Purdue (head linesman); Meyer, Ohio State (field judge)
In week nine, the Lions and Packers met for the third time in the 1935 season. This time, the Lions came out on top 20–10. Bill Shepherd, who had been acquired by the Lions in a trade for Doug Nott on November 4, 1935, scored two touchdowns for the Lions. Ebding added another. Dutch Clark kicked two extra points. The game was attended by 14,000 spectators at University of Detroit Stadium.
For their 11th game, the Lions played the Bears on Thanksgiving Day in Detroit. Dutch Clark scored two touchdowns as the Lions beat the Bears 14–2. The Bears scored a safety after Buddy Parker fumbled and recovered the ball behind his own goal line.
In their final regular-season game, the Detroit Lions defeated the Brooklyn Dodgers 28–0 in front of 12,000 spectators in Detroit. The Lions scored on a field goal by Glenn Presnell, a touchdown reception by Presnell, two safeties, and touchdowns by Dutch Clark and Ace Gutowsky. They scored 16 points in the fourth quarter. The win gave the Lions the undisputed NFL Western Division title.
Referee:Tommy Hughitt, Buffalo (referee), Tommy Cahn, Chicago (umpire), M. J. Mayer, Ohio Wesleyan (head linesman), H. D. Robb, Pittsburgh (field judge)
The 1935 NFL Championship Game was held on December 15, 1935, at University of Detroit Stadium (some sources call it Titan Stadium) in Detroit. The game was played in a snowstorm in front of 12,000 spectators. It was the 3rd annual title game for the NFL. The champion of the Western Division was the Detroit Lions (7–3–2) and the champion of the Eastern Division was the New York Giants (9–3). On the opening drive of the game, the Lions Glenn Presnell threw a 36-yard pass to Frank Christensen, and Ace Gutowsky threw another long pass to Ed Klewicki at the Giants' 8-yard line. Gutowsky then ran the ball into the end zone to give the Lions a 7–0 lead. The Lions scored again after Christensen intercepted a pass thrown by New York's Ed Danowski and ran it back to midfield. Three plays later, Dutch Clark ran 40 yards for a touchdown. In the fourth quarter, the Lions blocked a punt, and George Christensen recovered the ball on the Giants' 22-yard line. Ernie Caddel ran the ball in from the one-yard line for the Lions' third touchdown. The Lions added to their lead late in the game after Parker intercepted a pass from New York quarterback (and former University of Michigan star) Harry Newman on the Giants' 45-yard line and returned it to the nine-yard line. Buddy Parker ran for the touchdown as the Lions won the championship by a final score of 26–7.
After the NFL Championship Game, the Lions played a game against an NFL All-Star team on January 1, 1936. The game was attended by 11,000 spectators and marked the first NFL game to be played in Denver, Colorado. The Lions scored five touchdowns, including three in the third period, for a 33–0 victory.