Studies were conducted at six locations across North Carolina to determine tolerance of ‘Sunbelt’ grape (bunch grape) and muscadine grape (‘Carlos’, ‘Triumph’, ‘Summit’) to indaziflam herbicide. Treatments included indaziflam (0, 50, 73 g ai ha–1) or flumioxazin (213 g ai ha–1) applied alone in April, and sequential applications of indaziflam (36, 50, 73 g ai ha–1) or flumioxazin (213 g ai ha–1) applied in April followed by the same rate applied in June. No crop injury was observed across locations. Muscadine yield was not affected by herbicide treatments. Yield of ‘Sunbelt’ grape increased with sequential applications of indaziflam at 73 g ha–1 when compared to a single application of indaziflam at 50 g ha–1 or flumioxazin at 213 g ha–1 in 2015. Sequential applications of flumioxazin at 213 g ha–1 reduced ‘Sunbelt’ yield compared to a single application of indaziflam at 73 g ha–1 in 2016. Trunk cross-sectional area was unaffected by herbicide treatments. Fruit quality (soluble solids concentration, titratable acidity, and pH) for muscadine and bunch grape was not affected by herbicide treatments. Indaziflam was safe to use at registered rates and could be integrated into weed management programs for southern US vineyards.