We conducted a cross-sectional study from 2008 to 2009 to evaluate the occurrence of feral and wild cats and the risk of Toxoplasma gondii infection in terrestrial wildlife in a natural area in Illinois, USA. Felids are definitive hosts for T. gondii and cats are a key component of rural and urban transmission of T. gondii. We selected four forest sites within the interior of the park and four edge sites within 300 m of human buildings. Feline and wildlife occurrence in the natural area was determined with the use of scent stations, motion-detection cameras, and overnight live trapping. Based on scent stations and trapping, feral cats used building sites more than forest sites (scent stations: P=0.010; trapping: P=0.083). Prevalence of T. gondii antibodies was determined with the use of the indirect immunofluorescent antibody test (IFAT) with a titer of 1:25 considered positive; T. gondii antibodies were detected in wildlife at all sites. Wildlife species were classified as having a large home range (LHR) or a small home range (SHR), based on published estimates and using a cutoff of 100 ha. Small–home-range mammals had a higher prevalence of antibody to T. gondii (odds ratio [OR] =4.2; P=0.018) at sites with a high frequency of cat occurrence (defined as ≥9 cat occurrences across three detection methods); this finding indicates that feral cats are the most likely source of environmental contamination. Overall, the prevalence of antibody to T. gondii among LHR mammals was significantly higher than the prevalence among SHR mammals (OR=7.1; P<0.001). Small–home-range mammals are an essential part of T. gondii–antibody prevalence studies and can be used as sentinels for risk of disease exposure to humans and wildlife in natural areas. This study improves our understanding of ecologic drivers behind the occurrence of spatial variation of T. gondii within a natural area.