Herbicide resistance is a common occurrence in southern Australia. The evolution of herbicide resistance is influenced by the selection pressure placed on the weed species controlled by that herbicide. Results from resistance screening of ∼4500 annual ryegrass (Lolium rigidum Gaud.) samples were entered in a GIS database, together with several agricultural parameters used in the Australian Bureau of Statistics Agricultural Surveys. This allowed a study of the associations between mode of action of resistance, geographic distribution of resistance across southern Australia, and farming practices employed in particular regions. Cultivation was negatively associated with resistances in acetyl-CoA carboxylase (ACCase)-inhibiting cyclohexanedione and acetolactate synthase (ALS)-inhibiting herbicides. Higher proportions of wheat sown were associated with higher incidences of resistance. ACCase-inhibiting aryloxyphenoxypropionate and cyclohexanedione and ALS-inhibiting resistances were higher in those shires where soils were predominantly acidic. This study demonstrates the association between farm practice and the evolution of herbicide resistance. The analysis provides reinforcement to the principle of rotating chemical modes of action with non-chemical weed control measures to minimise the risk of herbicide resistance evolution in any farming system.