The problem of global warming and related climate change, as well as rising oil prices, is driving the implementation of ideas that not only reduce the consumption of liquid fuels, but also reduce greenhouse gas emissions. One of them is the use of natural gas as an energy source. It is a hydrocarbon fuel with properties allowing the reduction of CO2 emissions during its combustion. Therefore, solutions are being implemented that allow natural gas to be supplied to means of transport, which are trucks of various categories and purposes. This article presents the results of tests of an engine from a used semi-truck, to which an innovative compressed natural gas (CNG) supply system was installed. This installation (both hardware and software), depending on the engine operating conditions, enables mass replacement by natural gas (up to 90%) of the basic fuel—diesel oil. During the tests, on the basis of the obtained results, the influence of the diesel fuel/CNG exchange ratio under various engine operating conditions on the concentration of toxic CO2, CO, NO, NO2, CH4, C2H6, NMHC, NH3 and exhaust smoke was assessed. The test results confirm that, compared to conventional fueling, the diesel/CNG-fueled engine allows for a significant reduction in CO2 concentration even in a car operated for several years with diesel fuel and with high mileage. The use of a non-factory installation significantly increased the concentration of methane CH4, nitrogen dioxide NO2 and carbon monoxide CO in the exhaust gas. It was found that the smoke content and the temperature of exhaust gases did not decrease with increasing ratio of fuel replacement. The concentration of CO, NOX, CH4 and NMHC was increased, while the concentration of CO2, C2H6, NH3 and the consumption of diesel fuel by the engine, decreased significantly. The innovation of the research is based on the use of a modern and unique engine gas fuel system control system where the original fuel supply system with unit pumps is able to reduce diesel oil consumption by up to 90%.