Organic sweetpotato growers have limited effective weed management options, and most rely on in-season between-row cultivation and hand weeding, which are time consuming, are costly, and deteriorate soil quality. Studies were conducted at the Samuel G. Meigs Horticulture Research Farm, Lafayette, IN, and at the Southwest Purdue Agricultural Center, Vincennes, IN, in 2022 and 2023 to determine the effects of in-row plant spacing and cultivar selection on weed suppression and organic sweetpotato yield. The experiment was a split-split plot design, with in-row spacings of 20, 30, and 40 cm as the main plot factor, weeding frequency (critical weed-free period and weed-free) as the subplot factor, and sweetpotato cultivar (‘Covington’ and ‘Monaco’) as the sub-subplot factor. However, in 2022, we evaluated only in-row spacing and weeding frequency because of the poor establishment of ‘Monaco’. In 2023, sweetpotato canopy at 5 wk after transplanting (WAP) decreased as in-row spacing increased from 20 to 40 cm, and sweetpotato canopy cover of ‘Monaco’ (62%) was greater than that of ‘Covington’ (44%). In-row spacing did not affect weed density at 4, 5, and 6 WAP. As in-row spacing increased from 20 to 40 cm, total sweetpotato yield pooled across both locations in 2023 decreased from 30,223 to 21,209 kg ha−1 for ‘Covington’ and from 24,370 to 20,848 kg ha−1 for ‘Monaco’; however, jumbo yield increased for both cultivars. Findings from this study suggest that an in-row spacing of 20 cm may provide greater yield than the standard spacing of 30 cm for both ‘Monaco’ and ‘Covington’.