| | Day | Time | | Opponent | Score | |
| February |
| | 20 | 11:00AM | vs. | Campbellsville University | L-0-1 | |
| | Martin Methodist College Spring Meltdown Tournament - Pulaski, Tenn. |
| | | 3:00PM | vs. | Freed-Hardeman University | W-12-1 (5) | |
| | Martin Methodist College Spring Meltdown Tournament - Pulaski, Tenn. |
| | 21 | 10:00AM | @ | Martin Methodist | W-4-0 | |
| | Sophomore pitcher Autumn Allen throws a one hitter to lead No. 25 McKendree over No. 8 Martin Methodist |
| | | 12:00PM | vs. | Georgetown College | W-11-6 | |
| | Martin Methodist College Spring Meltdown Tournament - Pulaski, Tenn. |
| | 27 | 12:00PM | @ | Union University | L-0-6 | |
| | | Game 2 | @ | Union University | L-5-10 | |
| | 28 | 12:00PM | @ | Lambuth University | W-8-2 | |
| | | Game 2 | @ | Lambuth University | W-4-1 | |
| March |
| | 5 | 1:30PM | vs. | Missouri-St. Louis | L-2-11 (6) | |
| | | Game 2 | vs. | Missouri-St. Louis | L-1-6 | |
| | 12 | 9:30AM | vs. | Lee University | L-0-1 | |
| | Gulf Coast Invitational - Orange Beach, Ala. |
| | | 1:00PM | vs. | Grand View University | W-10-6 (8) | |
| | Gulf Coast Invitational - Orange Beach, Ala. |
| | 13 | 11:00AM | vs. | Oklahoma Christian University | W-6-0 | |
| | Gulf Coast Invitational - Orange Beach, Ala. |
| | | 2:30PM | vs. | Spring Hill College | W-6-4 | |
| | Gulf Coast Invitational - Orange Beach, Ala. |
| | 14 | 9:00AM | vs. | Martin Methodist | L-2-3 | |
| | Gulf Coast Invitational - Gulf Shores, Ala. |
| | | 11:30AM | vs. | Auburn University Montgomery | W-3-2 (9) | |
| | Gulf Coast Invitational - Gulf Shores, Ala. |
| | | 2:00PM | vs. | Faulkner University | W-4-1 | |
| | Gulf Coast Invitational - Gulf Shores, Ala. |
| | | 4:30PM | vs. | Martin Methodist | L-0-1 | |
| | Gulf Coast Invitational - Gulf Shores, Ala. |
| * | 17 | 2:00PM | vs. | Williams Baptist | W-1-0 | |
| * | | Game 2 | vs. | Williams Baptist | L-1-2 | |
| | 19 | 2:00PM | vs. | William Penn University | W-3-1 | |
| | McKendree Invitational - Lebanon, Ill. |
| | | 4:00PM | vs. | University of St. Mary | W-9-0 | |
| | McKendree Invitational - Lebanon, Ill. |
| | 20 | 10:00AM | vs. | William Penn University | W-5-0 | |
| | McKendree Invitational - Lebanon, Ill. |
| | | 2:00PM | vs. | University of St. Mary | W-10-1 (6) | |
| | McKendree Invitational - Lebanon, Ill. |
| * | 29 | 2:00PM | vs. | Stephens | W-3-0 | |
| | Katie Ward throws no-hitter for McKendree |
| * | | Game 2 | vs. | Stephens | W-7-0 | |
| * | 31 | 2:00PM | vs. | Missouri Baptist | W-7-2 | |
| * | | Game 2 | vs. | Missouri Baptist | W-8-0 | |
| April |
| * | 5 | 2:00PM | @ | Harris-Stowe | L-1-2 | |
| | Played at Saint Louis University |
| * | | Game 2 | @ | Harris-Stowe | L-3-5 | |
| | Played at Saint Louis University |
| * | 8 | 3:00PM | vs. | Hannibal-LaGrange | W-8-0 (5) | |
| | Katie Ward throws a no-hitter for McKendree |
| * | | Game 2 | vs. | Hannibal-LaGrange | W-4-0 | |
| | 9 | 1:00PM | vs. | Millikin University | W-9-0 (5) | |
| | Katie Ward throws second consecutive no-hitter - McKendree Invitational - April 9-11 |
| | | 5:00PM | vs. | Central Baptist College | L-0-6 | |
| | McKendree Invitational - Lebanon, Ill. - April 9-11 |
| | 10 | 10:00AM | vs. | Central Baptist College | L-0-9 (5) | |
| | McKendree Invitational - Lebanon, Ill. - April 9-11 |
| | | 2:00PM | vs. | Robert Morris College | W-2-1 | |
| | McKendree Invitational - Lebanon, Ill. - April 9-11 |
| | 11 | 9:00AM | vs. | Westminster College | W-9-0 | |
| | McKendree Invitational - Lebanon, Ill. - April 9-11 |
| | | 5:00PM | vs. | Missouri Valley College | W-1-0 | |
| | McKendree Invitational - Lebanon, Ill. - April 9-11 |
| * | 13 | 3:00PM | @ | William Woods | W-3-1 (8) | |
| * | | Game 2 | @ | William Woods | W-6-1 | |
| * | 17 | 2:00PM | @ | Park | L-1-5 | |
| * | | 4:00PM | @ | Park | W-7-4 | |
| | 18 | 12:00PM | @ | Avila University | W-4-0 | |
| | | Game 2 | @ | Avila University | W-8-2 | |
| * | 20 | 2:00PM | @ | Columbia | L-2-3 | |
| * | | Game 2 | @ | Columbia | L-0-4 | |
| | 23 | 12:00PM | vs. | Olivet Nazarene University | W-3-2 | |
| | McKendree Invitational - Lebanon, Ill. - April 23-24 |
| | 24 | 11:00AM | vs. | Robert Morris College | L-2-3 | |
| | McKendree Invitational - Lebanon, Ill. - April 23-24 |
| | 30 | 12:00PM | vs. | Hannibal-LaGrange | W-5-1 | |
| | 2010 AMC Softball Tournament Quarterfinals |
| | | Game 2 | vs. | Hannibal-LaGrange | W-5-0 | |
| | 2010 AMC Softball Tournament Quarterfinals |
| May |
| | 4 | 2:00PM | @ | Williams Baptist | W-4-3 | |
| | 2010 AMC Softball Tournament Semifinals |
| | | Game 2 | @ | Williams Baptist | W-1-0 | |
| | 2010 AMC Softball Tournament Semifinals |
| | 7 | 2:00PM | @ | Columbia | L-0-3 | |
| | 2010 AMC Softball Tournament Championship |
| | | Game 2 | @ | Columbia | L-0-2 | |
| | 2010 AMC Softball Tournament Championship |
