This study integrates diatom analysis with existing records of pollen, charcoal, elemental composition, and stable light isotopes to expand upon the 4200-year history of human activity and climate change from Laguna Los Mangos in southern Pacific Costa Rica. We counted diatoms in peroxide-treated samples and analyzed community composition using cluster analysis, revealing four distinct assemblage zones with diatom variability most closely correlated with phosphorus, titanium, and organic content. The earliest assemblage (Zone D, 4150–3430 cal yr BP) was dominated by Encyonema silesiacum and Nitzschia incognita and aligned with a period of deforestation, erosion, and abundant macrophytes. Gomphonema affine proliferated in Zone C (3430–2450 cal yr BP), reflecting increased pH and productivity likely caused by agriculture-induced nutrient loading. We attributed the preservation gap from 3290 to 2970 cal yr BP in Zone C to silica depletion and erosional deposition that induced decline in diatom abundance by diluting valve concentrations in lake sediments. Nitzschia incognita and G. affine became the dominant taxa in Zone B (2450–1400 cal yr BP), likely reflecting eutrophy, increasing conductivity, and drying climate. Dominance of Diadesmis confervacea indicated reduced lake level in Zone A (1400 cal yr BP–modern) at the onset of the Terminal Classic Drought (TCD). A hiatus in the record indicates lake desiccation from 950 to 450 cal yr BP. During the Little Ice Age (LIA), diatoms reflect conditions similar to Zone B indicating increased lake level, circumneutral pH, and eutrophy. Refilling of the lake indicates increased precipitation during the LIA despite evidence of severe regional drought reported at other sites. Variable precipitation during this period likely resulted from the combined effects of Spanish contact, agricultural collapse, forest recovery, and shifts in Atlantic and Pacific climate forcing mechanisms. Overall, the Los Mangos diatom record reflects shallow, slightly alkaline, eutrophic conditions influenced by nutrient enrichment, erosion, and deforestation associated with maize agriculture.