Fusarium wilt of watermelon can be effectively managed by grafting with resistant rootstocks. Excision and regeneration of grafted seedling roots is a common practice among cucurbit-grafting nurseries that has not been thoroughly examined. The objectives of this study were to compare the performance of grafted and nongrafted watermelon plants under both greenhouse and field conditions when inoculated with Fusarium oxysporum f. sp. niveum (FON) race 2, and assess the effect of root excision on growth of grafted plants with Cucurbita moschata and Cucurbita maxima × C. moschata rootstocks. Two greenhouse experiments (Fall 2015 and Spring 2016) and one field trial (Spring 2016) of seedless watermelon ‘Melody’ were conducted in this study. In both greenhouse experiments, inoculated, nongrafted watermelon plants showed a significantly higher percentage of recovered Fusarium spp. colonies (70% to 75%) compared with grafted treatments (0% to 7.5%). Some plant growth measurements, including the longest vine length and aboveground fresh and dry weight, indicated less vigorous growth for nongrafted plants compared with the grafted treatments. Significantly higher percent recovery of Fusarium spp. below the graft union was observed in the grafted plants with root excision and regeneration treatment (3.7%) in contrast to the intact root treatment (0.5%), suggesting that the root excision method may possibly create entry points for FON infections. Overall, the root excision treatment showed little influence on aboveground growth and root characteristics of grafted plants. Yield of grafted watermelon with FON inoculation in the fumigated field trial was significantly higher than that of noninoculated, nongrafted ‘Melody’ (NGM) control as reflected by the increase of fruit number and size. Averaged over all the grafted treatments, the increase in marketable fruit number and weight reached 108.3% and 240.9%, respectively, and the total fruit number and weight increase was at 80.0% and 237.2%, respectively. However, grafted plants also exhibited greater levels of root-knot nematode infestation as indicated by the significantly higher root galling ratings. Results from this study demonstrated that grafting with squash rootstocks can effectively limit FON colonization in seedless watermelon plants, although more research in rootstock selection and testing is needed to optimize the use of grafted plants for improving plant growth and fruit yield.