Abstract BACKGROUND Cultivation of grapes is a major crop globally, particularly in support of the wine production industry which has significant economic impact in numerous countries. Sour rot is an economically important disease of grapes. It is caused by an interaction of yeast + acetic acid bacteria, and vectored by Drosophila spp. Substantial control of sour rot in wine grape vineyards has been achieved by control of Drosophila using insecticides such as zeta‐cypermethrin. An outbreak of sour rot and high populations of Drosophila melanogaster were observed in 2018 in a vineyard in New York (Finger Lakes region), USA. Flies from this population were found to be resistant to zeta‐cypermethrin (the active ingredient in Mustang Maxx®), but whether or not this was a widespread problem was not known. To determine if resistance was geographically limited, we surveyed populations of D. melanogaster collected from 11 vineyards across New York State and one in Missouri (USA). We also evaluated 19 alternative insecticides for their potential use for control of D. melanogaster , by determining their toxicity to a susceptible strain and by examining cross‐resistance using a field‐collected population. RESULTS There were high levels of resistance to zeta‐cypermethrin, malathion, and acetamiprid found in all populations sampled. Resistance to zeta‐cypermethrin and malathion was stable over 33 months. Results from two vineyards also suggested that resistance to spinetoram was starting to evolve. The alternative insecticides we evaluated had LC 50 values to the susceptible strain ranging from 0.65 to 15 000 ng·cm −2 . CONCLUSION Resistance to zeta‐cypermethrin, malathion, and acetamiprid is geographically widespread and the levels of resistance are similar between early season and late season collections. Cross‐resistance was detected against all the insecticides tested, with the lowest levels seen for broflanilide, fipronil, and flumethrin. These patterns of resistance/cross‐resistance/multiple resistance are discussed in terms of selection within and outside of vineyards. The implications of these results to insecticide resistance monitoring and management are discussed.