The paper deals with the experimental study of a medium-load spark ignition engine under operation with different fuel mixtures among those deemed as promising for the transition towards carbon-free energy systems. In particular, the performance of a non-conventional ignition system, which permits the variation of the ignition energy, the spark intensity and duration, was studied fuelling the engine with 60–40% hydrogen–methane blends, three real syngas mixtures and one biogas. The paper is aimed to find the optimal ignition timing for minimum specific fuel consumption and the best setup of the ignition system for each of the fuel mixtures considered. To this end, a series of steady-state tests were performed at the dynamometer by varying the parameters of the ignition system and running the engine with surrogate hydrogen–methane–nitrogen mixtures that permit the simulation of hydrogen–methane blends, real syngas, and biogas. The results quantify the increase of spark advance associated with the decrease of the fuel quality and discuss the risk of knock onset during methane–hydrogen operation. It was demonstrated that the change of the ignition system parameters does not affect the value of optimum spark advance and, except for the ignition duration, all the parameters’ values are generally not very relevant at full load operation. In contrast, at partial load operation with low-quality syngas or high exhaust gas recirculation rate, it was found that an increase of the maximum ignition energy (to 300 mJ) allows for operation down to approximately 66% of the maximum load before combustion becomes incomplete. Further reductions, down to 25% of the maximum load, can be achieved by increasing the gap between the spark plug electrodes (from 0.25 to 0.5 mm).