Background: Foot and mouth disease (FMD) and enterotoxaemia are serious livestock diseases. The livestock industry has suffered heavy economic losses, especially in developing countries. Objectives: These two diseases can be effectively controlled and prevented via vaccination. To prepare multivalent vaccines, Clostridium perfringens (B, C, and D) toxoids were mixed with foot and mouth disease virus (FMDV; type O) along with adjuvants aluminum hydroxide and Montanide ISA206. Methods: According to the guidelines of the World Organization for Animal Health (OIE) and pharmacopeia, sheep were the target animals. Following the injection of vaccines, ELISA and virus neutralization test (VNT) antibody titers determined the effectiveness of the test vaccines. Results: The combination vaccine with ISA206 adjuvant resulted in anti-enterotoxaemia and anti-FMD antibody titers higher than OIE values and pharmacopeia standards. A statistically significant difference was found between the combination vaccine groups with and without Montanide ISA206 adjuvant for anti-enterotoxaemia antibody titers after the second vaccination (P < 0.05). In contrast, the mean VNT antibody titer of the combined vaccine against serotype O with ISA206 adjuvant was significantly higher than that of other FMD vaccine groups (P < 0.05). Moreover, all vaccinated groups (A, B, C, D, E, Fand G) displayed significantly higher than the negative control group (P < 0.05). Conclusions: This study showed that enterotoxaemia-FMD combined vaccines could replace traditional livestock vaccines on an industrial scale.