Hypoxia on the Louisiana continental shelf is tied to nutrient loading and freshwater stratification from the Mississippi River. Variations in the relative abundance of low-oxygen-tolerant benthic foraminifers in four sediment cores from the Louisiana shelf provide a proxy record of low-oxygen events. Core chronologies are obtained using 210Pb dating techniques. The foraminiferal data are consistent with previous studies indicating that the intensity of hypoxic events (oxygen <2 mg/L) has increased over the past 50 yr owing to the higher nutrient loading associated with the use of commercial fertilizer, and also reveal several low-oxygen events between A.D. 1817 and 1910, prior to the widespread use of fertilizer. The pre-1910 low-oxygen events are associated with high Mississippi River discharge rates, indicating that these low-oxygen episodes are related to natural variations in river drainage that enhance transport of nutrients and freshwater to the continental shelf. Our data show that the low-oxygen events of the past few decades were more extreme than any that occurred in the previous ∼180 yr, and support the interpretation that the increased use of fertilizer has amplified an otherwise naturally occurring process.