This paper assesses the potential of a single HYSPIRI scene to estimate cover of the non-native invasive buffelgrass (Pennisetum ciliare) in a heterogeneous Sonoran Desert scrub ecosystem. We simulated HYSPIRI (60 m) along with two multispectral sensors, Thematic Mapper (TM; 30 m) and Advanced Space-borne Thermal Emission and Reflection Spectrometer (ASTER; 15 m), from high-resolution Airborne Visible/Infrared Imaging Spectrometer (AVIRIS; 3.2 m) imagery in an area infested by buffelgrass near Tucson, Arizona. We compared classification accuracies of all simulated sensors at spatial resolutions of 15 m, 30 m, and 60 m to evaluate tradeoffs of spectral and spatial resolution across the sensors. Although spectroscopically superior to Landsat TM and ASTER, ASTER easily outperformed HYSPIRI for small infestations (225 m2) on account of its spatial resolution. Shortwave-infrared bands near 2.2 µm were key indicators for both HYSPIRI and ASTER, highlighting the benefit of narrow-wave SWIR for mapping invasive species in arid ecosystems.