To open the 1941 season, Alabama defeated the Southwestern Louisiana Institute Bulldogs (now known as the Louisiana–Lafayette Ragin' Cajuns) 54–0 at the Cramton Bowl on a Friday night. After Don Salls recovered a Bobby Voitier fumble on the Bulldogs' opening possession, Salls scored Alabama's first touchdown of the night on a 30-yard run on the possession that ensued. The Crimson Tide then extended their lead to 14–0 at the end of the first quarter after Russ Mosley threw a 47-yard touchdown pass to George Weeks. In the second quarter, Alabama scored a trio of touchdowns on Kenny Reese runs of 7 and 24-yards and on a 45-yard Norman Mosley run to make the halftime score 35–0. The second half saw many of Alabama's reserves play and three more touchdowns. In the third-quarter touchdowns were scored by Joe Domnanovich on a 25-yard interception return and on an Al Sabo reception. The Crimson Tide got their final points in the fourth quarter on a 2-yard Lou Scales touchdown run. The victory improved Alabama's all-time record against the Bulldogs to 2–0.
In the first conference game of the season, Alabama defeated Mississippi State 21–6 in what was the first conference loss for the Maroons since the 1939 season. After a scoreless first half, Russ Craft scored all three of the Crimson Tide's touchdowns in the third quarter on runs of 3, 38 and 4-yards. Mississippi State responded in the fourth quarter with their only points of the afternoon on a 43-yard Billy Murphy touchdown pass to Kermit Davis to make the final score 21–6. The victory improved Alabama's all-time record against Mississippi State to 20–7–2.
With the outbreak of World War II, many leaders in the military viewed football as a means to help develop leadership abilities and greater discipline in preparation for combat. As such, during this time colleges scheduled military schools and organizations for regular season football games. For their third game of the season, Alabama met the team that represented the Naval Air Station Pensacola at Mobile, and defeated the Goslings 27–0. The game also marked the first for Alabama against a service team since the 1917 season. In the game, Alabama scored a touchdown in all four quarters and outgained Pensacola in rushing yards 295 to minus 2. Touchdowns were scored by Russ Craft on a 3-yard run in the first, on a 5-yard Johnny August pass to Al Sabo in the second, Craft on a 6-yard reverse in the third and on a 39-yard Kenny Reese run in the fourth.
After each team opened the season undefeated through the fourth week, Alabama entered the first AP Poll of the season as No. 4 team and Tennessee entered as the No. 15 team. Due to each team being ranked and the heated rivalry between each other, NBC broadcast the game nationally over 218 radio affiliates and Bill Stern served as commentator. In the game, Alabama defeated the Volunteers 8–0 before 25,000 fans at Legion Field. After a scoreless first half, the Crimson Tide scored their first points of the game on the opening kickoff of the second half. Alabama took a 2–0 lead after Bob Cifers was tackled in the endzone for a safety. The only touchdown of the contest was scored in the fourth quarter on a 38-yard Tom Jenkins run. The victory improved Alabama's all-time record against Tennessee to 15–8–2.
After their victory over Tennessee, Alabama moved up one position to the No. 3 spot in the AP Poll prior to their game at Kentucky. On what was homecoming in Lexington, the Crimson Tide shutout the Wildcats 14–0. After a scoreless first half, touchdowns were scored by Russ Mosley on a 2-yard run in the third and by Lou Scales on a 1-yard run in the fourth. The victory improved Alabama's all-time record against Kentucky 20–1–1.
As both Alabama and Georgia were undefeated as they entered their game, both received top five rankings in the weekly AP Poll. Although the Crimson Tide led 10–0 at the start of the fourth quarter, three late touchdowns gave the Bulldogs the 21–10 victory at Grant Field in Atlanta.Russ Craft scored first for Alabama with his 47-yard touchdown run in the first quarter. Alabama then extended their lead to 10–0 early in the third quarter when George Hecht kicked a 20-yard field goal. In the fourth quarter, the Bulldogs staged their comeback to win the game 21–10. Fourth-quarter touchdowns were scored on Frank Sinkwich passes of 5 and 13-yards to George Poschner and by Andrew Dudish on a 25-yard fumble return. The loss brought Alabama's all-time record against Georgia to 14–12–3.
After their loss to Georgia, the Crimson Tide dropped five places to the No. 8 position in the weekly AP Poll prior to their game against South Carolina. On homecoming at Denny Stadium, Alabama defeated the Gamecocks 29–0. Alabama took a 13–0 first quarter lead after Johnny August connected on touchdown passes of 24-yards to Kenny Reese and 38-yards to James Roberts. They then scored their final 16 points of the game in the second quarter on a 44-yard Russ Craft touchdown run, and 84-yard Dave Brown touchdown run and when the Gamecocks' Ken Roskie was tackled for a safety. The victory improved Alabama's all-time record against South Carolina to 2–0.
Prior to their second trip to Atlanta of the season, this time to face Georgia Tech, Alabama moved up from the No. 8 position to the No. 5 position in the AP Poll. Against the Yellow Jackets, the Crimson Tide was shutout 7–0 at Grant Field in a game that saw two dominant defenses. The only points of the game came in the first quarter when Ralph Plaster scored for Georgia Tech on a short run. The loss brought Alabama's all-time record against Georgia Tech to 13–12–3.
After their loss against Georgia Tech, Alabama dropped down spots to the No. 9 position in the AP Poll prior to their game against Vanderbilt. Against the Commodores, Alabama rebounded from their loss to the Yellow Jackets with a 27–7 victory at Legion Field. First half touchdowns were scored by Johnny August on an 11-yard run in the first quarter and on a 1-yard Tom Jenkins run in the second quarter. The Crimson Tide extended their lead to 27–0 in the third quarter with touchdowns scored on a 5-yard Dave Brown run and on a 45-yard Bill Baughman interception return. The Commodores ended the shutout for the Alabama defense in the fourth quarter when Jack Jenkins scored on a 5-yard touchdown run. The victory improved Alabama's all-time record against Vanderbilt to 14–10.
After their victory over Vanderbilt, Alabama moved up two spots to the No. 7 position in the AP Poll prior to their game against Georgia Pre-Flight. Against the Skycrackers, Alabama lost 35–19 at Legion Field to a team that featured several former college stars in addition to former Crimson Tide player and future coach Bear Bryant. The Skycrackers took a 7–0 lead in the first quarter after Thomas White blocked a Russ Mosleyquick kick that was returned 40-yards by Darrell Tully for a Georgia touchdown. Tully then scored the second touchdown on a 9-yard run in the second quarter to cap a 70-yard drive and give the Skycrackers a 14–0 halftime lead. Georgia extended their lead further to 28–0 at the end of the third quarter with touchdowns on a 25-yard Frank Filchock pass to Bob Foxx and on a Jim Poole reception. In the fourth quarter, Alabama scored first on a 3-yard Don Salls touchdown run to cut the Georgia lead to 28–6. The Skycrackers responded with a 9-yard Filchock to Poole touchdown pass to extend their lead to 35–6. Alabama did score the final pair of touchdowns in the game on a 19-yard Tom Jenkins run and on a 21-yard Norman Mosley pass to Jim McWhorter to make the final score 35–19.
After their loss to Georgia Pre-Flight in their regular season finale, on November 30 Alabama accepted an invitation to play in the Orange Bowl against the Boston CollegeEagles. At that time, the final AP Poll was also released with Alabama in the No. 10 position and Boston College in the No. 8 position. In the Orange Bowl, the Crimson Tide overcame a 14–0 first quarter deficit to defeat the Eagles 37–21. Boston College took a 14–0 lead with first-quarter touchdowns scored on a 65-yard Mike Holovak pass to Ed Doherty and on a 33-yard Holovak run. Alabama responded with three consecutive touchdowns in the second quarter to take a 19–14 lead on a 14-yard Russ Mosley pass to Wheeler Leeth, a 17-yard Johnny August pass to Ted Cook and on a 40-yard Tom Jenkins run. The Eagles then scored their final points of the game on a 1-yard Holovak touchdown run before the Crimson Tide took a 22–21 halftime lead on a 15-yard George Hecht field goal. Alabama went on to shutout the Eagles in the second half and score on a 15-yard August run in the third and on a 1-yard Jenkins run in the fourth. Joe Domnanovich then tackled Harry Connolly for a safety to make the final score 37–21.