This study evaluated the effect of a yeast beta-glucan on the performance, gut health, liver function, and bacterial translocation of broiler chickens fed a diet contaminated with Fusarium mycotoxins. One-day-old male Ross broilers (n = 234) were divided into three treatments with six replicates each, and a cage containing 13 birds was the experimental unit. The animals were fed a maize-soybean-based control diet or maize-soybean diets naturally contaminated with Fusarium mycotoxins, where deoxynivalenol (DON) was the major mycotoxin (similar to 3 mg/kg), followed by zearalenone (ZEN) (similar to 0.5 mg/kg). The Fusarium-contaminated diet was either supplemented or not with a yeast beta-glucan over 28 days. Dietary exposure to Fusarium mycotoxins did not affect production performance. On the other hand, Fusarium mycotoxin exposure significantly decreased jejunum villus height (VH) and crypt depth (CD) on d13, and this effect was counteracted by the yeast beta-glucan. On d28, the jejunum VH:CD ratio was significantly higher in the broiler chickens that were fed the Fusarium-contaminated diet with yeast beta-glucan (125 mg/kg diet) added to it. The ileal villus area was significantly decreased in the broiler chickens fed Fusarium-contaminated diet, regardless of the supplementation with yeast beta-glucan. Dietary contamination caused intestinal oxidative stress and inflammation, probably affecting nutrient absorption on d28, and resulted in a significant increase in the translocation of Escherichia coli to the liver. Dietary supplementation with yeast beta-glucan minimized these negative effects.