Black-grass (Alopecurus myosuroides) is one of the most problematic agricultural weeds of Western Europe, causing significant yield losses in winter wheat (Triticum aestivum) and other crops through competition for space and resources. Previous studies link black-grass patches to water-retaining soils, yet its specific adaptations to these conditions remain unclear. We designed pot-based waterlogging experiments to compare 13 biotypes of black-grass and six cultivars of wheat. These showed that wheat roots induced aerenchyma when waterlogged whereas aerenchyma-like structures were constitutively present in black-grass. Aerial biomass of waterlogged wheat was smaller, whereas waterlogged black-grass was similar or larger. Variability in waterlogging responses within and between these species was correlated with transcriptomic and metabolomic changes in leaves of control or waterlogged plants. In wheat, transcripts associated with regulation and utilisation of phosphate compounds were upregulated and sugars and amino acids concentrations were increased. Black-grass biotypes showed limited molecular responses to waterlogging. Some black-grass amino acids were decreased and one transcript commonly upregulated was previously identified in screens for genes underpinning metabolism-based resistance to herbicides. Our findings provide insights into the different waterlogging tolerances of these species and may help to explain the previously observed patchiness of this weed’s distribution in wheat fields.