It is important to understand the altitude adaptability of the turbocharging system for maximizing its potential in the power recovery of the diesel engine at high altitudes. This study investigated the influence of altitudes ranging from 0 to 4500 m on the performance of the single-stage and two-stage turbocharging systems in a heavy-duty diesel engine. The research was conducted using a six-cylinder, four-stroke, turbocharged, direct-injection diesel engine. An altitude simulation test bench was used to simulate altitudes of 0 to 4500 m by adjusting the temperature and pressure. According to the test results, the altitude adaptability of different turbocharging systems was analyzed based on turbine work and turbocharger efficiency. It was concluded that the high-pressure stage regulation in the two-stage turbocharging system (HRT) strengthens the regulation ability in turbine work, effectively regulating the boost pressure and maintaining high turbocharger efficiency at different altitudes. The HRT can satisfy the regulation ability for altitudes ranging from 0 to 4500 m. The low-pressure stage regulation in the two-stage turbocharging system (LRT) weakens the regulation ability in turbine work and relies on reduction of the turbocharger efficiency to regulate the boost pressure. The LRT ineffectively regulates the boost pressure at low altitudes, with altitude adaptability from 1500 to 4500 m. Due to the exhaust temperature limitation, the waste-gate in the single-stage turbocharging system (WG) is not suitable for large-span regulation to satisfy the performance of the diesel engine at altitudes above 3,000 m compared with the HRT and LRT.