Iowa State Agricultural College (Iowa State University) played its first organized game of football against State Center (1892) under coach and team captain Ira Brownlie. Football had been played at Iowa State since the 1870s, but only on an intramural level. In 1894, the team became part of an officially organized athletic association and competed with other colleges in the state of Iowa.

Iowa State football began playing on the west side of central campus, first behind Old Main (where Beardshear Hall is located), then north of Marston Hall (known as State Field). In 1914, "New" State Field was completed at the northeast corner of Sheldon and Lincoln Way. This location was later named Clyde Williams Field and served as the home of Cyclone football until 1974. Cyclone Stadium, later renamed Jack Trice Stadium, opened at the Iowa State Center (1975) and is the current home of the program.

The "Cyclone" nickname came from a game Iowa State played at Northwestern in 1895. Iowa State beat what was a well-regarded Wildcats team, 36-0 and the Chicago Tribune had a headline the next day that read "Struck By A Cyclone" in reference to a tornado that had devastated the Iowa town of Grinnell a year earlier. The Cyclone name has been associated with Iowa State ever since.

Early football legend and innovator, Glenn "Pop" Warner, coached Iowa State football, several weeks each year from 1895 through 1899. During his first two years with Iowa State, he simultaneously coached the University of Georgia's football team. Other prominent names from college football coaching history to have passed through Ames include former head coaches Johnny Majors (1968-1972) and Earle Bruce (1973-1978), and assistant coaches Jimmy Johnson (1968-1969), Jackie Sherrill (1968-1972), Pete Carroll (1978), and Mack Brown (1979-1981). Dan McCarney has the most wins of any coach in Iowa State history with 56.

In the Johnny Majors era, Iowa State went to its first bowl game, a 33-15 loss against Louisiana State University in the Sun Bowl (1971). The first Cyclone bowl win came at the Insight.com Bowl against Pittsburgh, 37-29 (2000). Iowa State has appeared in ten bowl games through the 2009 season, winning three (2000, 2004, and 2009).

Iowa State has had a history of post-season recognition for players and coaches. There have been four Heisman Trophy finalists: Dwight Nichols, 8th place (1959); George Amundson, 7th place (1972); and Troy Davis, 5th place (1995) and 2nd place (1996). Earle Bruce was selected Big 8 Coach of the Year (1976 and 1977) and Dan McCarney was voted Big 12 Coach of the Year (2001and 2004)

Through the 2009 season, Iowa State football has an overall win-loss-tie record of 488-580-46.

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