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Abstract Efforts to reduce the frequency, extent, and toxicity of harmful algal blooms (HABs) require knowledge about drivers of algal growth, toxin production, and shifts in phytoplankton community composition to cyanobacterial dominance. Although labile nitrogen (N) and phosphorus (P) fuel primary production, micronutrients also play roles as the enzymatic engines that facilitate rapid and efficient growth and toxin production. Macro‐ and micronutrient availability can shape community composition and function by selecting for particular taxa. To address how phytoplankton in two Great Lakes subbasins respond to macro‐ and micronutrients, we conducted bottle incubation enrichment experiments using water collected from two blooming and two nonblooming sites in Lakes Erie and Michigan during late summer (August). Three of the four sites exhibited multi‐nutrient limitation of growth. Both blooming sites responded strongest to enrichment. Both nonblooming sites responded the strongest to enrichment, and three of the four sites responded in some way to a mix of micronutrients (Fe, Mn, Mo, Ni, and Zn).Microcystis aeruginosarelative abundance increased most with N enrichment, while P enrichment increased the abundance of diatoms and chlorophytes. At the Fox River, N‐enriched communities grew 10%–20% more than non‐N enriched communities (measured as chlorophylla), and N‐enriched communities had, on average, over twice as much microcystin (non‐N communities average MC = 2.45 μg · L⁻¹, +N communities MC = 5.35 μg · L⁻¹). These overarching trends support the idea that control of HABs may not be effective with a P‐only approach.