The invasiveness of nonnative taxa can vary across a landscape due to environmental gradients, suggesting that location-dependent management strategies may be more effective at reducing spread compared to a “one size fits all” approach across the entire introduced range. Using bait stations placed along linear transects within habitat preserves, we tested for effects of ecoregion, vegetation, soil moisture, habitat edge type (i.e., moisture source), and distance from edges on the presence of the invasive Argentine ant Linepithema humile in San Diego County, California, a region with high indigenous biodiversity and numerous rare and protected species. Our results showed an inverse relationship between the presence of native ant species and the presence of the Argentine ant across ecoregions, with the latter reaching peak abundance in the coastal terrace. Argentine ant presence was negatively associated with distance from all edge types regardless of location, but the magnitude of this effect varied among ecoregions. In the xeric foothill and inland valleys, the probability of occurrence was nearly 0 at distances of 200 m and 750 m from moisture edges, respectively, whereas in the coastal terrace, the probability remained above 0.80 at distances up to 1.25 km. When compared to previous studies at different spatial scales, these findings provide an alternative perspective on the invasiveness of the Argentine ant at the landscape level. Our results further suggest that efforts to control spread in regions with a Mediterranean climate may be more successful in inland areas, where the ant is likely to have lower environmental tolerance and native ant species may be better able to generate biotic resistance. In contrast, different tactics and expectations may be necessary for coastal areas, where the same constraints are diminished or absent.