Efficiency is a concept that evaluates the optimal utilization of resources, including time, energy, finances, or materials, in order to accomplish a particular goal or objective. As widely acknowledged, energy losses occur in systems involving relative motion between interacting machine elements due to friction. In the case of a gearbox, these losses can arise from tooth friction in the gear mechanism, friction in sealing elements, friction in roller bearings, and the influence of the lubricant used in the system, all of which are subject to environmental conditions. This study aims to experimentally determine the efficiency of the gearbox under various operating conditions by considering the gearbox as a comprehensive system encompassing all its components. A measurement system was designed in order to obtain the efficiency of a gearbox. Experiments and measurements were carried out via software support. The measurement system contains two torque transducers, electrical resistive load device, an electrical motor with temperature measurement thermocouple, and two stage helical gearbox. In experiments conducted through computer commands, input revolutions were incrementally increased with 400 rpm intervals within the range of 700–2700 rpm. Moreover, experiments were carried out at different lubricant levels in the gearbox. At the same time lubricant temperature was measured and effects to the gearbox efficiency were investigated. Subsequently, different lubricant with distinct viscosity indices were employed. As a result of this experimental design, regime efficiency values were obtained for each case. Thus, power loss of the gearbox system has been determined. These results were examined using a general full factorial design. Analysis of variance (ANOVA) tables were created and the effects of the parameters on the system and the efficiency results were determined by checking whether the parameters were interacting or not. Finally, regression analysis was performed and the regression function was obtained in order to develop a predictive model to estimate the efficiency of a gearbox.