The team most notably defeated northern power Carlisle by a single Bob Blake field goal 4–0.

Notable losses from the 1905 team included Bachelor of Ugliness Ed Hamilton, captain Innis Brown,[2] and quarterback Frank Kyle.

Football was a sport that had degenerated into dangerous tactics such as: the flying wedge, punching, kicking, piling-on, and elbows to the face.

[5] The rules governing intercollegiate football were changed to promote a more open and less dangerous style of play.

An intercollegiate conference, which would become the forerunner of the NCAA, approved radical changes including the legalization of the forward pass, allowing the punting team to recover an on-side kick as a live ball, abolishing the dangerous flying wedge, creating a neutral zone between offense and defense, and doubling the first-down distance to 10 yards, to be gained in three downs.

[6] [16] Sources:[17] In a 28–0 win over Kentucky State College to open the season, Owsley Manier scored three touchdowns and the Commodores as a whole rushed for 630 yards.

[5] One account reads: "whatever hopes the spectators had of seeing a close and exciting football game today when Vanderbilt faced Mississippi were shattered in the very first five minutes of play.

[23] Owsley Manier scored five touchdowns[18] as: "the back field frequently went twenty-five or thirty yards over the line".

McGugin and Yost both spoke to the crowd and agreed that the game would be one of the closest played in Ann Arbor in many years.

Early in the second half, Vanderbilt tied the score with a field goal by Dan Blake from the 30-yard line.

The Chicago Daily Tribune wrote: "Garrels, on a fake kick, with splendid interference by Hammond, Curtis, and Workman, ran Vanderbilt's left end at lightning speed for sixty-eight yards and a touchdown."

[30] Sources:[31] Vanderbilt defeated coach John Heisman, who had helped legalize the forward pass, and his Georgia Tech team in the rain and mud of Atlanta 37–6.

[31] Sources:[32] On Thanksgiving, the Commodores reached the season's high point and beat the Carlisle Indians 4–0.

[36] Frank Mount Pleasant, one of the first regular spiral pass quarterbacks,[37] attempted four field goals, but missed them all.

Pleasant in his tracks on most of Blake's punts...I am still convinced that outside Yale and Princeton, the Commodores would have an even break with any other team in the country.

"[40] Vanderbilt running back Honus Craig called this his hardest game, giving special praise to Albert Exendine as: "the fastest end I ever saw.

[32] Sources:[43] Despite Vanderbilt's strong record, the Sewanee Tigers were undefeated and felt cause for optimism in the effective Southern championship.

One account recalls: "A high authority on foot-ball said the other day: Vanderbilt is not invincible, by a good deal.

[46] Coach McGugin called the Carlisle victory "the crowning feat of the Southern Intercollegiate Athletic Association season.

"But his effectiveness at Pennsylvania was lessened by the attempt of the coaches to change his style of bucking a line from the low, plunging dive to running into it erect, knees drawn high and great dependence upon his companion backs to "hike" him.

[51] Pritchard coached at LSU for part of one season and was later a Presbyterian dental missionary at Luebo in the Congo until he was forced to return to the United States due to poor health sometime before 1915.

"[55] The following chart provides a visual depiction of Vanderbilt's lineup during the 1906 season with games started at the position reflected in parentheses.