Understanding the factors driving past fire regimes is crucial in the context of global change as a basis for predicting future changes. In this study, we aimed to identify the impact of climate and human activities on fire occurrence in the most fire-prone regions of Switzerland. We considered forest fires, land use and meteorological data over the period 1904–2008 in the neighboring mountain cantons (states) of Valais and Ticino, which are characterized by distinct climatic regimes. The presence/absence of fire ignitions was analyzed using the Nesterov ignition index (as a proxy for fire weather), road density (for ignition sources), livestock density (for biomass removal), and change in forest area (for fire-prone abandoned agricultural areas). We found that fire weather played a key role in fire occurrence in both regions. Road and livestock densities had similar influences in the two cantons. However, while the increase in forest area was well correlated with fire occurrence in Ticino, no such correlation was evident in Valais, probably because land abandonment and forest cover change have been less extensive there. Our findings emphasize the non-linear nature of the relationships between fire occurrence and anthropogenic drivers, as we found thresholds above which road density was no longer correlated with fire occurrence. This implies that the projected future increase and spatial concentration of the human population may not result in a further increase in fire risk in intermediately to densely populated areas in both cantons. The driving factors behind fire activity differ slightly in the two cantons, in particular with increasing forest area enhancing fire occurrence in Ticino but not in Valais. These differences should be taken into account when assessing future fire risk, especially in Valais where the potential for an increase in the fire-prone area is still high. Fires are likely to become more frequent in a warmer climate, but future fire activity may develop differently in the two cantons. This should be taken into account when planning optimized fire prevention measures. This case study should help to better understand fire activity in highly populated regions where fire activity is still moderate but might markedly increase under a projected more fire-prone climate