Cultivated plants have been selected by humans for increased yield in a relatively benign environment, where nutrient and water resources are often supplemented, and biotic enemy loads are kept artificially low. Agricultural weeds have adapted to this same benign environment as crops and often have high growth and reproductive rates, even though they have not been specifically selected for yield. Considering the competing demands for resources in any plant, a key question is whether adaptation to agricultural environments has been accompanied by life history trade-offs, in which resistance to (largely absent) stress has been lost in favour of growth and reproduction. The experiments reported here were designed to test for growth-defence trade-offs in agricultural weeds, crops and native varieties of common sunflower (Helianthus annuus L., Asteraceae) by comparing their performance in the presence or absence of abiotic (drought and crowding) or biotic (simulated herbivory, insect herbivory and fungal) stress. We found that growth, as well as viability of crops and weeds, was reduced by abiotic drought stress. The weakened defence in the agricultural genotypes was further evident as increased susceptibility to fungal infection and higher level of insect palatability. To uncover molecular mechanisms underlying these trade-offs, we monitored gene expression kinetics in drought-stressed plants. By correlating phenotypic observations with molecular analyses, we report the identification of several genes, including a protein phosphatase 2C and the HD-Zip transcription factor Athb-8, whose expression is associated with the observed phenotypic variation in common sunflower.