Bethel's head coach Travis Graber resigned on July 27, 2012 with just over a month before the season begins for his team.

Baker University from the Heart of America Athletic Conference traveled to Ottawa and Tabor visited Bacone College of the Central States Football League.

With 1:49 left to play, Ryder Werts fell on the ball in the end zone for a touchdown and kicker Steven Stewart made the extra point to put the Wildcats up by seven.

[12] Ottawa began the game without offensive starter Matt Bollig, who suffered a career-ending injury during weightlifting practice in July.

Tabor showed heart in the third quarter by scoring 20 points and made a good attempt at a comeback,[16] but allowed Bacone to tack on an additional 12 to win the game 25–20.

[17] The games of week 1 produced only one non-conference victory with Bethany, who took sole possession of first place in the conference standings and a record of 1–0.

[18] Tenth ranked Northwestern hosted the Southwestern College Moundbuilders on a Thursday night game in front of 2,347 fans.

[21] Bethel's interim coach James Dotson had just 41 players suited up for their season opener, against 14th-ranked William Penn.

[24] Kansas Wesleyan met #22 Cumberland in the "Big River Bowl" hosted in Dyersburg, Tennessee, the first of two games played that day at the location.

[29] Saint Mary's Jerrell Young caught a 9-yard pass from Mike Keese for a touchdown in the first quarter to get off to a 7–0 lead.

Wesleyan's Nate Hauptman made good on a 1-yard run for a touchdown in the second quarter to tie up the score, but Saint Mary pulled ahead when Marcus Mata ran for a four-yard touchdown and Saint Mary went in at halftime with a 14–7 lead.

[30] Saint Mary's top-flight passing attack helped give the Spires a 458-242 edge in total offense.

[22] Saint Mary still held a thin lead when Wesleayn's Nate Hauptman threw a 30-yard pass to Ryan Larsen for a touchdown because the extra point was blocked.

[30] Nebraska Wesleyan scored on three straight possessions in the second half and batted down a fourth-and-goal pass in the end zone to hold on for the win.

[22] Saint Mary attempt to come back in the fourth quarter fell short and Nebraska Wesleyan won 25–20.

The team returned 13 starting players for the new season, including quarterback Reid Golson and running backs Sean Haynes and Cade Leuschner.

[34] Bethany's Darby House managed to throw two touchdown passes to offset SAGU's four field goals.

[36] Underdog Kansas Wesleyan ended the first quarter with a 17–7 lead and held it for the remainder of the game, although 11th-ranked Ottawa did manage to work up what looked like a comeback.

The difference came down to kicking, as Kansas Wesleyan's Terry Stecker managed a field goal to put the Coyotes far enough ahead to keep the victory.

Cunningham made good on the extra point for the second time and the result was a McPherson upset over #24 Bethany by a score of 14–0.

[41] The game was cancelled in light of the ongoing investigation into the murder of Tabor football player Brandon Brown.

[44] Both were on the football roster at McPherson for the previous year, and Franklin was listed as a sophomore linebacker at the beginning of the 2012 season.

[47] After a preliminary hearing on January 31, 2013, the suspects Franklin and Flournoy were bound over for trial on charges of being accessories to second-degree murder.

[48] The McPherson County Medical Examiner testified that Brown's blood alcohol level was .30, well above the legal limit in the state of Kansas.

[49] DeQuinte Flournoy later changed his position and entered a plea of no contest to a reduced charge of felony aggravated battery.

[55] At the end the regular season play, the conference granted multiple individual and team awards.

Friends University's Derek Racette earns Special Teams Player of the Year and Jordan Barrett of Southwestern College was named the "Dr. Ted Kessinger Champion of Character Award" recipient.