Across a small geographic area (<180 km), the region of South-West Greenland covers a natural climate gradient. Variation in temperature and precipitation result in marked differences in limnology at three discrete locations: ice sheet margin, inland, and the coast. Replicate lakes from each location were sampled for physical (temperature, light), chemical (dissolved oxygen, pH, conductivity, nutrients), and biological (chlorophyll a [Chl a], photosynthetic pigments) variables on three occasions within a 12-month period: July–August 2010, April–May 2011, and June–July 2011 spanning ice cover. Variation in ice phenology was linked to the climate gradient; however, phytoplankton production and community composition did not differ regionally. Large-scale seasonal fluctuations in temperature and nutrient availability were the strongest predictors of phytoplankton production, with a shift from nitrate to phosphorus controlled production between ice-cover and ice-free conditions. Underlying seasonal drivers, variables predicting production were unique to each location—ice sheet margin (soluble reactive phosphorus), inland (temperature), and coast (silicate)—and reflect local differences in nutrient availability. Results from the current study have important consequences when controls over phytoplankton production in Arctic lakes are inferred from a limited number of sites, but up-scaled to represent pan-Arctic trends.