Soil waterlogging and subsequent ethylene release from cotton (Gossypium hirsutum L.) tissues has been linked with abscission of developing cotton fruits. This glasshouse study investigates the effect of a 9-day waterlogging event and CO2 enrichment (eCO2, 700 parts per million (ppm)) on a fully linted cultivar 'Empire' and a lintless cotton mutant (5B). We hypothesised that cotton performance in extreme environments such as waterlogging can be improved through mitigating ethylene action. Plants were grown at 28:20°C day:night temperature, 50-70% relative humidity and a 14:10 light:dark photoperiod under natural light and were exposed to waterlogging and eCO2 at early reproductive growth. Ethylene synthesis was inhibited by spraying aminoethoxyvinylglycine (830ppm) 1 day before waterlogging. Waterlogging significantly increased ethylene release from both cotton genotypes, although fruit production was significantly inhibited only in Empire. Aminoethoxyvinylglycine consistently reduced waterlogging-induced abscission of fruits, mainly in Empire. Limited damage to fruits in 5B, despite increased ethylene production during waterlogging, suggested that fruit abscission in 5B was inhibited by disrupting ethylene metabolism genetically. Elevated CO2 promoted fruit production in both genotypes and was more effective in 5B than in Empire plants. Hence 5B produced more fruits than Empire, providing additional sinks (existing and new fruit) that enhanced the response to CO2 enrichment.