While extant literature has generally indicated significant associations between vegetation cover and tick activity, no study has demonstrated the relative association between peri-domestic area vegetation cover subtypes and tick presence. In this study, we seek to determine whether neighborhood wood index and residential tick control practices confound or modify the effect of peri-domestic vegetation cover subtypes on tick presence. We conducted an ecological inventory of vegetation cover distribution using i-Tree Canopy on 210 private residential/peri-domestic properties in Indiana, USA. Results were paired with field obtained tick presence/absence data for each property together with online survey data provided by primary occupant of the property. Amblyomma americanum was the predominant tick species in peri-domestic areas. Higher proportion of vegetation cover in the peri-domestic area was significantly associated with tick presence. Of the four vegetation cover subtypes, (grass, shrubs, understory, and canopy), canopy was the most prevalent vegetation in peri-domestic areas of Indiana, USA. It was also the most significant predictor of tick presence. Among residential tick control processes, frequent leaf litter removal was significantly associated with reduced likelihood of peri-domestic tick presence. Neighborhood Wood Index (NWI) confounded the relationship between canopy and peri-domestic tick presence, while leaf-litter removal confounded the effect of understory vegetation subtype on peri-domestic tick presence. Compared to peri-domestic areas in neighborhoods with sparse NWI, those in neighborhoods with heavy/dense NWI had a 3.5x odd of peri-domestic tick presence (AOR = 3.46; 95 % CI: 1.23–9.65). Compared to peri-domestic areas in the central region, those in the southern region of Indiana were 8.7x more likely to have peri-domestic tick presence. Canopy as a vegetation cover subtype and frequent leaf litter removal represent particularly key peri-domestic variables that have significant implications for peri-domestic tick presence. Beyond parcel-scale landscape features, neighborhood wood index also plays an important role in peri-domestic tick presence. Additionally, i-Tree Canopy represents a promising methodological tool for identifying landscape features that predict tick presence.