The production of clean energy via carbon-neutral fuels has been included in a road map within several international institutions. Among the available alternatives, hydrogen has been largely considered as one of the most promising solutions. However, technologies for its safe storage and optimized combustion are still under development or on a prototypal stage. Hence, the addition of hydrogen to less reactive fuels has been proposed as a supplementary route for short and mid-term solutions. A self-evident example of this trend is the design of infrastructures transporting mixtures of natural gas and hydrogen in a ratio up to 3:1 on a molar basis. In most cases, the addition of hydrogen to pure methane has been considered, so far, narrowing the beneficial effects on the environmental perspective. Indeed, the utilization of bio-derived methane may help to broaden these positive aspects. Nevertheless, the effects of the initial composition on chemical and thermal aspects are still poorly understood. In this perspective, the characterization of the overall reactivity and severity in case of accidental release in terms of laminar burning velocity represents an appealing solution. For these reasons, this work presents a detailed analysis of coupling experimental and numerical investigations to fully understand the involved phenomena. More specifically, the overall reactivity was measured for gaseous mixtures representative for bio-derived methane enriched by hydrogen, at first. Several compositions and initial temperatures were examined at this stage. Then, the validity of a theoretical-based mechanism was tested against experimental data, allowing for further characterization of the investigated species. The most prominent effects of operative conditions on the ignition phenomena were numerically individuated and discussed. The results collected throughout this work provide a robust feature for the detailed evaluation of the normal operations as well as the accidental release of hydrogen-containing fuels.