It is important to use the most appropriate plant cultivar in restoration or biofuel trials especially when plantings are likely to be invaded by undesirable species. In this study, the competitive response of two lowland and three upland cultivars of the dominant C₄ grass Panicum virgatum to three invasive species (Bromus inermis, Schedonorus phoenix, and Poa pratensis) was tested using a simple pair-wise greenhouse experiment. Response variables (height, number of leaves, tiller density, and biomass of P. virgatum) and resources (soil moisture and light intensity) were measured over a seven-month period. Performance of the different P. virgatum cultivars were differentially reduced by the three invasive species, especially the performance of the Kanlow (lowland) and Blackwell (upland) cultivars. Low soil moisture reduced the performance of P. virgatum in the presence of only one invasive (Bromus inermis) irrespective of cultivar source. Root, shoot, and total biomass depended on cultivar and did not show an interaction with invasive species identity. The results of this greenhouse study suggest that the P. virgatum cultivars differentially responded to the invasive species and that the cultivar used should be considered carefully in planning prairie restorations or biofuel trials in the context of likely invasive species.