Diesel engines are the predominant power source for the trucking industry. Heavy-duty trucks carry more than 70% of all goods transported across the United States. Atmospheric conditions vary with altitude but are critical to diesel engine performance, efficiency, and emissions. Existing studies have reported reduced thermal efficiency and increased emissions when truck engines were operated at high altitudes. Since heat loss is a key parameter related to engine efficiency, the goal of this paper was to investigate the altitude impacts on the in-cylinder heat transfer characteristics. Experiments on a single-cylinder four-stroke heavy-duty diesel engine were conducted at a constant speed and load, but with different intake pressures to simulate the varying atmospheric conditions at different altitudes. The quantity of diesel fuel injected into the cylinder per cycle was increased to maintain the same power output at decreased atmospheric pressure and to compensate for the combustion deterioration that occurred inside the cylinder. Experimental results showed that the bulk temperature was higher at high altitudes because of less mass of the mixture trapped in the cylinder. Such a large temperature difference between the hot products and the cold walls increased the in-cylinder heat transfer to the coolant, especially during combustion. Specifically, the 2000 m altitude rise led to an increase in heat loss to the atmosphere of ∼2% per cycle under full load conditions. As a result, the application of thermal coatings to improve fuel economy is even more necessary in high altitude states, such as Colorado and Wyoming.