Background: Campylobacter is a common, but neglected foodborne-zoonotic pathogen, identified as a growing cause of foodborne disease worldwide. Wildlife and domestic animals are considered important reservoirs, but little is known about pathogen infection dynamics in free-ranging mammalian wildlife particularly in sub-Saharan Africa. In countries like Botswana, there is significant overlap between humans and wildlife, with the human population having one of the highest HIV infection rates in the world, increasing vulnerability to infection. Methodology/Principal findings: We investigated Campylobacter occurrence in archived human fecal samples (children and adults, n = 122, 2011), feces from free-ranging banded mongooses (Mungos mungo, n = 201), surface water (n = 70), and river sediment samples (n = 81) collected in 2017 from the Chobe District, northern Botswana. Campylobacter spp. was widespread in humans (23.0%, 95% CI 13.9–35.4%), with infections dominantly associated with C. jejuni (82.1%, n = 28, 95% CI 55.1–94.5%). A small number of patients presented with asymptomatic infections (n = 6). While Campylobacter spp. was rare or absent in environmental samples, over half of sampled mongooses tested positive (56%, 95% CI 45.6–65.4%). Across the urbanwilderness continuum, we found significant differences in Campylobacter spp. detection associated with the type of den used by study mongooses. Mongooses utilizing man-made structures as den sites had significantly higher levels of C. jejuni infection (p = 0.019) than mongooses using natural dens. Conversely, mongooses using natural dens had overall higher levels of detection of Campylobacter at the genus level (p = 0.001). Conclusions: These results suggest that landscape features may have important influences on Campylobacter species exposure and transmission dynamics in wildlife. In particular, data suggest that human-modified landscapes may increase C. jejuni infection, a primarily human pathogen, in banded mongooses. Pathogen circulation and transmission in urbanizing wildlife reservoirs may increase human vulnerability to infection, findings that may have critical implications for both public and animal health in regions where people live in close proximity to wildlife.