Catchment land uses, particularly agriculture and urban uses, have long been recognized as major drivers of nutrient concentrations in surface waters. However, few simple models have been developed that relate the amount of catchment land use to downstream freshwater nutrients. Nor are existing models applicable to large numbers of freshwaters across broad spatial extents such as regions or continents. This research aims to increase model performance by exploring three factors that affect the relationship between land use and downstream nutrients in freshwater: the spatial extent for measuring land use, hydrologic connectivity, and the regional differences in both the amount of nutrients and effects of land use on them. We quantified the effects of these three factors that relate land use to lake total phosphorus (TP) and total nitrogen (TN) in 346 north temperate lakes in 7 regions in Michigan, USA. We used a linear mixed modeling framework to examine the importance of spatial extent, lake hydrologic class, and region on models with individual lake nutrients as the response variable, and individual land use types as the predictor variables. Our modeling approach was chosen to avoid problems of multi-collinearity among predictor variables and a lack of independence of lakes within regions, both of which are common problems in broad-scale analyses of freshwaters. We found that all three factors influence land use-lake nutrient relationships. The strongest evidence was for the effect of lake hydrologic connectivity, followed by region, and finally, the spatial extent of land use measurements. Incorporating these three factors into relatively simple models of land use effects on lake nutrients should help to improve predictions and understanding of land use-lake nutrient interactions at broad scales.