High-altitude cities like Sangolquí, Ecuador (2000–2500 m.a.s.l.) present a double challenge for vehicle performance: reduced engine output due to lower air density and the frequent use of air conditioning (A/C) to maintain thermal comfort in warm conditions. While various authors have conducted theoretical analyses of A/C power consumption in different regions and climates, this study complements them by incorporating practical measurements through chassis dynamometer testing and real-world driving fuel consumption trials. A thermodynamic model estimated the A/C compressor’s demand at 2.89 hp., while experimental results showed a total power loss of 4.85 hp., including mechanical inefficiencies. Combined with the estimated 30% power reduction due to altitude, the A/C’s impact on performance becomes highly significant. Fuel economy testing under urban (15–40 km/h) and highway (70–100 km/h) conditions indicated that driving with windows down is more fuel-efficient in city environments. At the same time, A/C use is preferable at higher speeds. These findings support the development of efficient driving strategies to reduce fuel consumption without sacrificing cabin comfort in high-altitude regions and contribute valuable insights for shaping public energy efficiency policies aimed at reducing emissions in challenging conditions. Additionally, future studies should consider testing other vehicle types, such as turbocharged or hybrid models, and account for compressor-specific losses to isolate better the combined impact of A/C use and altitude on performance.