This study aimed to investigate the effect of the prophylactic feeding of Clostridium butyricum (CB), Saccharomyces cerevisiae (SC), and their mixture before the onset of heat stress on the rumen fermentation and growth performance of goats, and subsequently, on heat stress status. Forty-eight male Macheng Black × Boer crossed goats (22.25 ± 4.26 kg) were divided into four groups—the control group (fed the basal diet), and the CB (0.05% CB added to the basal diet), SC (0.60% SC added to the basal diet), and Mix (0.05% CB and 0.60% SC added to the basal diet) groups—and fed for fourteen days. Then, these goats were kept in a heat stress environment (with a temperature–humidity index of 87.04) for fourteen days. Then, the parameters of rumen fermentation and growth performance were measured. The results showed that the pH values, the activities of cellulolytic enzymes (avicelase, CMCaes, cellobiase, and xylanase), and the concentrations of ammonia-N, total volatile fatty acid, acetic acid, propionic acid, and butyric acid were significantly increased (p < 0.05) in the rumens of the CB, SC, and Mix groups compared to those of the control group. Moreover, the average daily gain and the digestibility of dry matter, neutral detergent fiber, and acid detergent fiber were significantly increased (p < 0.05) in the CB, SC, and Mix groups compared to those of the control group. These results suggest that these two probiotics and their mixture effectively alleviate the adverse effects of heat stress on rumen fermentation and growth performance via prophylactic feeding.