The recent expansion of cannabis agriculture in rural areas of the western United States provides an ideal opportunity to study the outcomes of rapid land use change for wildlife. Small scale (<1 acre), private-land cannabis cultivation has the ability to impair or coexist with surrounding wildlife communities. This study examines local wildlife community dynamics on and surrounding active private-land cannabis farms in the Klamath-Siskiyou Ecoregion in southern Oregon. Using camera data collected between 2018–2019, we modeled the space use of medium to large mammals as a function of distance to cannabis farm, using both single- and multi-species occupancy frameworks. We found that wildlife had differential responses to cannabis farms. In general, larger-bodied mammals seemed to respond more strongly to cannabis farms, but there was evidence for relatively fine scale thresholds of effect. These results add to the growing understanding of wildlife response to human disturbance, particularly in frontier development scenarios. This study highlights the need for further research on site-level production practices and their influence on surrounding ecological communities.