Non-deforestation fire – i.e., fire that is typically followed by the recovery of natural vegetation – is arguably the most influential disturbance in terrestrial ecosystems, thereby playing a major role in carbon exchanges and affecting many climatic processes. The radiative effect from a given atmospheric CO2 perturbation is the same for fire and fossil fuel combustion. However, major differences exist per unit of CO2 emitted between the effects of non-deforestation fire vs. fossil fuel combustion on the global carbon cycle and climate, because (1) fossil fuel combustion implies a net transfer of carbon from geological reservoirs to the atmospheric, oceanic, and terrestrial pools, whereas fire occurring in terrestrial ecosystems does not; (2) the average lifetime of the atmospheric CO2 increase is longer when originating from fossil fuel combustion compared to fire, due to the strong vegetation regrowth following fire disturbances in terrestrial ecosystems; and (3) other impacts, for example on land surface albedo, also differ between fire and fossil fuel combustion. The main purpose of this study is to illustrate the consequences from these fundamental differences between fossil fuel combustion and non-deforestation fires using 1000-year simulations of a coupled climate–carbon model with interactive vegetation. We assessed emissions from both pulse and stable fire regime changes, considering both the gross (carbon released from combustion) and net (fire-caused change in land carbon, also accounting for vegetation decomposition and regrowth, as well as climate–carbon feedbacks) fire CO2 emissions. In all cases, we found substantial differences from equivalent amounts of emissions produced by fossil fuel combustion. These findings suggest that side-by-side comparisons of non-deforestation fire and fossil fuel CO2 emissions – implicitly implying that they have similar effects per unit of CO2 emitted – should therefore be avoided, particularly when these comparisons involve gross fire emissions, because the reservoirs from which these emissions are drawn have very different residence times (millions of years for fossil fuel; years to centuries for vegetation and soil–litter). Our results also support the notion that most net emissions occur relatively soon after fire regime shifts and then progressively approach zero. Overall, our study calls for the explicit representation of fire activity as a valuable step to foster a more accurate understanding of its impacts on global carbon cycling and temperature, as opposed to conceiving fire effects as congruent with the consequences from fossil fuel combustion.