Straub threw for 352 yards for the Salukis (4-3, 2-2 Missouri Valley Conference). Daquan Isom ran for 73 yards and two scores — one rushing, one receiving — and Darrell James had 154 yards and a score receiving.
Straub threw over-the-middle scoring passes to James and to Connor Iwema in the first quarter to help Southern Illinois to a 24-14 halftime lead.
The Salukis led the rest of the way, with Straub adding a short TD pass to Isom late in the third quarter and D.J. Davis and Jonathan Mixon adding rushing scores in the fourth.
The Sycamores (0-7, 0-4) scored on a pass interception by Rondell Green with 8:17 left in the fourth quarter but a fumble ended their next drive and the Salukis defense remained firm in the final minutes.
Isaac Harker had 206 yards and a score passing with two interceptions for Indiana State.