Zach Copeland scored 24 points to lead the Redbirds (6-14, 1-7), who stretched a 23-17 halftime lead to 29-19 with 17:14 left. Jaycee Hillsman added 11 points for ISU.
Freshman Marcus Domask paced the Salukis (11-10, 5-3) with 19 points, including 16 in the second half. Domask's back-to-back 3-pointers gave SIU a 52-48 lead that ISU couldn't overcome.
Copeland's 3-pointer to tie in the final seconds hit the side of the backboard.
It was SIU's first victory at Redbird Arena since the 2006-07 season.
ISU entertains Evansville at 7 p.m. Wednesday at Redbird Arena.
