The Cyclones competed as members of the Big 12 Conference and were led by fourth-year head coach Matt Campbell.

In January 2019, head coach Matt Campbell announced that Tom Manning would return as offensive coordinator.

[2] He had served in that role for the Cyclones in Campbell's first two years in 2016 and 2017, but worked as the tight ends coach for the Indianapolis Colts during the 2018 season.

In the Big 12 preseason media poll, Iowa State was predicted to finish in third in the standings.

[5] Referee Scott Campbell Both Iowa State and Oklahoma lost their previous games.