In his junior season of 2004, Humber compiled a 13–4 win–loss record and 2.27 ERA. He struck out 154 batters and issued only 37 walks in 115 innings. He also set the Rice single-game record for strikeouts when he struck out 17 Hawaii Rainbow Warriors hitters on March 20, 2004. Rice entered the 64-team NCAA Baseball tournament as one of the eight national seeds. In the first game of the regional round of the tournament, Rice was upset by the Texas Southern Tigers. Humber entered the next game against the Texas A&M Aggies with the bases loaded and surrendered a first-pitch grand slam to Justin Ruggiano. For the season, Humber totaled 154 strikeouts in 115 innings pitched.