Former guard coach Luther Richards left the squad in September and Harold Klein stepped in temporarily while finishing his degree.

[16] Dick Fullerton resigned to go into business and Bill Daddio signed a contract to play football for the Chicago Cardinals.

[23][17] On October 4, the Panthers opened the season against Mal Elward's Purdue Boilermakers, the supposed weakest of their 4 Western Conference opponents.

The Pitt offense then advanced the ball to the Purdue 22-yard, from where they threw five incomplete passes (off-setting penalties gave the extra down) as time ran out in the first half.

Substitutes appearing in the game for Pitt were Norbert Gestner, Jack Durishan, Joseph Broudy, Steve Sinclair, Ralph Fife, Joe Salvucci, John Stahl, Ralph Hammond, Edgar Jones, Joe Connell, Frank Saska, Jack Kerr and Mat Gebel.

[5] On October 11, the Pitt Panthers traveled to Ann Arbor, MI for their first game against Fritz Crisler's Michigan Wolverines in “The Big House”.

Michigan scored 6 touchdowns, had one called back on a clipping penalty, and ran out of time on the Pitt 1-yard line to end the game.

[31] The 40–0 defeat was the worst drubbing handed the Panthers since 1903 when the WUP athletic department was in disarray and both Penn State (59–0) and Geneva (57–0) ran up the score.

Substitutes appearing in the game for Pitt were John Stahl, Norbert Gestner, Martin Rosepink, Jack Durishan, Joe Salvucci, Robert Crissman, Vince Antonelli, Joseph Broudy, William Dillon, Steve Sinclair, James Clowes, Ralph Hammond, George Allshouse, Frank Scatton, Edgar Jones, Joe Connell, Frank Saska, Jack Kerr and Mat Gebel.

[42] Bowser told the Star Journal: "I'd say our morale is good under the circumstances and the changes we have made in the lineup this week have improved our team somewhat, but I'm not going to hazard any guess on what will happen until I see for myself.

[45] The Minnesota Gophers finished the season unbeaten and were named National Champions in the final Associated Press football poll for the second year in a row.

A Walter West fumble recovered by center Bob Barnett gave Duke possession on the Panthers' 26-yard line.

Substitute running back William Dutton gained 48 of the yards on seven carries, but John Ross broke through center from the 2-yard line for the touchdown.

[54] Prior to the Pitt game Coach Brown dismissed starting left end Charley Anderson from the squad for disobeying team rules.

[55] Coach Bowser's new lineup gave the Buckeyes a battle, but the Ohio eleven prevailed and kept the Panthers winless with a 21 to 14 victory.

Ohio guard George Cheroke broke through the Panthers' line and blocked a Jones punt into the end zone.

Substitutes appearing in the game for Pitt were Michael Sotak, Harry Kindelberger, William Dillon, Joseph Broudy, Vincent Antonelli, Harold Hinte, Martin Rosepink, Ralph Hammond, Jack Stetler,and Joe Connell.

Jim Crowley's Rams had outscored their previous opponents 115–38, and, as 8–1 favorites with a #3 ranking in the AP poll, were favored to win their remaining games and return to a bowl.

[58][59] Fordham led the all-time series 2–1–3, and due to Pitt's football de-emphasis, this was the final meeting on the gridiron between the two schools.

In the fourth quarter, Edgar "Special Delivery" Jones intercepted a Benny Babula pass and raced 33 yards for the second touchdown.

Eleven plays later Bill Dutton bulled into the end zone from the 1-yard line, and Ralph Fife converted the point after to tie the score.

Pitt back Edgar "Special Delivery" Jones intercepted Bradley's pass and raced 75 yards for a touchdown.

Nebraska went to the air again and Jones intercepted an errant Howard Debus pass and raced 48 yards before he was tackled on the 3-yard line as time ran out.

Substitutes appearing in the game for Pitt were Jack Durshan, George Mitchell, Steve Sinclair,Vincent Antonelli, Martin Rosepink, Ralph Hammond, Harold Stickel and William Dutton.

[79] Tartan coach Eddie Baker's squad numbered only 23 and his best running back, Virgil Cantini, was injured and would not play.

[81] Fifteen seniors were playing their final game as Panthers – Al Kunkel, Ralph Fife, Stan Gervelis, Joe Connell, John Ross, Hap Stickel, Ray Rabinek, Stave Sinclair, Bill Benghouser, John Stahl, Robert Crissman, Harry Kindelberger, George Mitchell, George Allshouse and Edgar Jones.

[89] Halfback Edgar "Special Delivery" Jones received honorable mentions on both the International News Service and United Press All-American football teams.

Coach Carl Snavely chose Jones for the North squad in the annual North-South All-Star game on Christmas Day.

[89] Coaches Andy Kerr and Bernie Bierman chose Fife and end Stanley Gervelis to play for the East squad in the annual East-West Shrine Game in San Francisco on New Year's Day.

After the attack on Pearl Harbor, the game was moved to Tulane Stadium in New Orleans and played on January 3, 1942 for security reasons.