Local-scale fire regimes are controlled by climate, fuel availability, and topography. Research on long-term (i.e., Holocene timescales) fire activity in the Northwest Territories has focused on local fire dynamics, with fewer studies examining regional patterns. To investigate the impacts of climate variability on wildfire activity during the Holocene, 13 macroscopic charcoal and 3 pollen records, as well as insolation values, reconstructed temperatures, and precipitation data were analyzed to understand the interactions of climate, regional fire regimes and vegetation during the Holocene in the North Slave Region, Northwest Territories, Canada. Following deglaciation, wildfire activity across the region was low, due to lack of fuels, relatively low temperatures, and dry conditions. By ∼8200 cal yrs. BP, wildfire activity increased across the region as Picea expanded on the landscape increasing fuel availability and summer temperatures increased and peaked during the Holocene Thermal Maximum. Wildfire activity continued to increase throughout the mid-Holocene until cooler and wetter conditions developed with the onset of Neoglacial cooling around 4200 cal yrs. BP. With the onset of cooler and wetter conditions, wildfires declined regionally across the North Slave Region. The decline in wildfire activity following Neoglacial cooling can be attributed to a general decline in temperatures and changes in vegetations types and density. During the 20th century, wildfire activity increased in response to warming temperatures. With further increases in global mean temperature, it is expected that wildfire activity in the North Slave Region will increase during the 21st century.