This study investigates the effect of oil viscosity on pollutant emissions and fuel consumption of an internal combustion engine (ICE) at high altitudes using a response surface methodology (RSM). A Chevrolet Corsa Evolution 1.5 SOHC gasoline engine was used in Cuenca, Ecuador (2560 m above sea level), testing three lubricating oils with kinematic viscosities of 9.66, 14.08, and 18.5 mm2/s, measured at a temperature of 100 °C under various engine speeds and loads. Key findings include the following: hydrocarbon (HC) emissions were minimized from 150.22 ppm at the maximum load to 7.25 ppm with low viscosity and load; carbon dioxide (CO2) emissions peaked at 15.2% vol with high viscosity and load; carbon monoxide (CO) ranged from 0.04% to 3.74% depending on viscosity and load; nitrogen oxides (NOx) were significantly influenced by viscosity, RPM, and load, indicating a need for model refinement; and fuel consumption was significantly affected by load and viscosity. RSM-based optimization identified optimal operational conditions with a viscosity of 13 mm2/s, 1473 rpm, and a load of 78%, resulting in 52.35 ppm of HC, 13.97% vol of CO2, 1.2% vol of CO, 0 ppm of NOx, and a fuel consumption of 6.66 L/h. These conditions demonstrate the ability to adjust operational variables to maximize fuel efficiency and minimize emissions. This study underscores the critical role of optimizing lubricant viscosity and operational conditions to mitigate environmental impact and enhance engine performance in high-altitude environments.