Powdered infant formula (PIF) can be contaminated with Cronobacter sakazakii, which can cause severe illnesses in infants. Synbiotics, a combination of probiotics and prebiotics, could act as an alternative control measure for C. sakazakii contamination in PIF and within the infant gut, but synbiotics have not been well studied for their ability to inhibit C. sakazakii. Using a Simulator of the Human Intestinal Microbial Ecosystem (SHIME®) inoculated with infant fecal matter, we demonstrated that a potential synbiotic, consisting of six lactic acid bacteria (LAB) strains and Vivinal GOS, can inhibit the growth of C. sakazakii in an infant possibly through either the production of antimicrobial metabolites like acetate, increasing species diversity within the SHIME compartments to compete for nutrients or a combination of mechanisms. Using a triple SHIME set-up, i.e., three identical SHIME compartments, the first SHIME (SHIME 1) was designated as the control SHIME in the absence of a treatment, whereas SHIME 2 and 3 were the treated SHIME over 2, 1-week treatment periods. The addition of the potential synbiotic (LAB + VGOS) resulted in a significant decrease in C. sakazakii levels within 1 week (p < 0.05), but in the absence of a treatment the significant decline took 2 weeks (p < 0.05), and the LAB treatment did not decrease C. sakazakii levels (p ≥ 0.05). The principal component analysis showed a distinction between metabolomic profiles for the control and LAB treatment, but similar profiles for the LAB + VGOS treatment. The addition of the potential synbiotic (LAB + VGOS) in the first treatment period slightly increased species diversity (p ≥ 0.05) compared to the control and LAB, which may have had an effect on the survival of C. sakazakii throughout the treatment period. Our results also revealed that the relative abundance of Bifidobacterium was negatively correlated with Cronobacter when no treatments were added (ρ = −0.96; p < 0.05). These findings suggest that C. sakazakii could be inhibited by the native gut microbiota, and inhibition can be accelerated by the potential synbiotic treatment.