Background/Objectives: Mycoplasma hyopneumoniae (Mhp), porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) are major contributors to porcine respiratory disease complex (PRDC), causing substantial economic losses. Methods: This study evaluated a commercial PCV2-Mhp bivalent vaccine, Cirbloc^® M Hyo (Vaccine A), containing recombinant PCV2 Cap protein and inactivated Mhp antigen, vs. two reference bivalent vaccines (B and C) in an Mhp challenge model. Eighty-two healthy 3-week-old specific-pathogen-free piglets were randomly allocated to five groups (three vaccinated, unvaccinated challenged control, unvaccinated unchallenged control). Pigs received a single intramuscular vaccination at 3 weeks of age and were challenged intratracheally with virulent Mhp lung homogenate five weeks later. Clinical signs, serology, lung lesions, histopathology, and Mhp DNA detection in lungs were assessed. Results: No vaccine-related adverse reactions occurred. Vaccine A induced earlier and higher Mhp-IgG seroconversion before challenge than reference vaccines. Following challenge, Vaccine A significantly reduced mean lung lesion scores compared with the unvaccinated challenged control (2.28 ± 2.37 vs. 6.56 ± 4.03; p < 0.05), with markedly reduced peribronchiolar inflammation and lymphoid hyperplasia and the lowest Mhp DNA detection rate among challenged groups. Conclusions: Cirbloc^® M Hyo provided enhanced protection against experimental Mhp challenge, as shown by reduced lung lesions and milder histopathological changes, supporting its use for comprehensive PRDC management.