Mora went 2-for-4 with three RBIs and Jose Lopez went 3-for-3 with a walk and scored twice for Venezuela.
Right-hander Felix Hernandez allowed a single in four scoreless innings to earn the victory. He walked two and struck out four.
Venezuela can advance to the second round with a victory over the United States on Sunday night. Italy will seek to avoid elimination from Group C when it meets host Canada on Monday night.
Mark DeFelice pitched four scoreless innings for Italy. Venezuela broke through in the fifth against Colorado right-hander Jason Grilli.
Guillen led off with a homer to left and Lopez followed with a double. After Ramon Hernandez flied out and Cesar Izturis walked, Italian manager Marco Mazzieri brought in left-hander Lenny DiNardo, but the move backfired when Endy Chavez reached on a bunt single, Mora drove in a run with a bases-loaded walk and Abreu singled through the right side, scoring two more.
Chicago Cubs right-hander Alessandro Maestri came on to end the rally, getting Miguel Cabrera on a fielder's choice and striking out Magglio Ordonez looking for the final out.
Mora led off the seventh with a drive into the second deck in left against Cody Cillo. Venezuela capped the scoring in the eighth when Lopez and Hernandez hit back-to-back doubles and, two outs later, Mora singled home Hernandez.
Italy wasted scoring chances in the early innings against Venezuelan starter Carlos Silva. Michael Costanzo was caught in a rundown after a leadoff double in the second, and Minnesota second baseman Nick Punto grounded back to the mound for the final out, stranding runners at second and third.
Silva worked four shutout innings, allowing six hits. He walked one and struck out two.
Baserunning errors also cost Venezuela early on. Lopez was thrown out trying to stretch a single into a double in the second, and Abreu was thrown out at third base when he ran too far past the bag after advancing on a fly ball in the fourth.
Italy's right fielder Mario Chiarini made the defensive play of the night, a full-stretch diving catch on Abreu's one-out liner in the first. Chiarini broke his belt on the play and had to run into the first-base dugout for a replacement.
NOTES: Toronto Raptors center Andrea Bargnani threw out the first pitch. ... Abreu was hit on the right thigh in the seventh. He stayed in to run the bases but was replaced by Gerardo Parra in the outfield to begin the eighth. ... Venezuela beat Italy 6-0 in the opening round of the 2006 World Baseball Classic.
Venezuela's Endy Chavez (47) is congratulated by teammates including Magglio Ordonez (30), Miguel Cabrera (24) and coach Roberto Espinoza, right, after scoring during the fifth inning of a World Baseball Classic game against Italy in Toronto on Satur
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