The objective of this research was to determine the potential use of commercially available multispectral images to detect weeds at low densities during the critical period of weed control. Common lambsquarters seedlings were transplanted into plots of glyphosate-resistant corn at 0, 1, 2, and 4 plants/m2 at two sites, Agronomy Center for Research and Extension (ACRE) and Meig's Horticultural Research Farm at the Throckmorton–Purdue Agricultural Center (TPAC), in Indiana. Aerial multispectral images (12 to 16 cm pixel resolution) were taken 18 and 32 days after planting (DAP) at ACRE and 19 and 32 DAP at TPAC. Corn and common lambsquarters could not be reliably detected and differentiated at either site when weeds were 9 cm or less in height. However, economic threshold densities (2 and 4 plants/m2) of common lambsquarters could be distinguished from weed-free plots at TPAC when weeds were 17 cm in height. At this height, common lambsquarters plants were beyond the optimal height for glyphosate application, but could still be readily controlled with higher rates. Results from this study indicate that commercially available multispectral aerial imagery at current spatial resolutions does not provide consistently reliable data for detection of early season weeds in glyphosate-resistant corn cropping systems. Additional refinement in sensor spatial and spectral resolution is necessary to increase our ability to successfully detect early season weed infestations.