Microcystin-LR (MC-LR), a toxin produced during some cyanobacterial harmful algal blooms (cyanoHABs), can harm ecosystems and require consideration in water treatment. Ultraviolet (UV)-C treatment has the potential to degrade cyanotoxins with less harmful byproducts than other treatments. This study compares MC-LR degradation in three different water types using UV-C light emitted from a krypton-chlorine excimer lamp (UV light at 222 nm, UV₂₂₂) or a low-pressure (LP) Hg lamp (UV light at 254 nm, UV₂₅₄). Quantitative analyses by enzyme-linked immunosorbent assay (ELISA), ultra-performance liquid chromatography with photodiode array detection (UPLC-PDA), and high-performance liquid chromatography-high-resolution mass spectrometry (LC-HRMS) demonstrated that UV₂₂₂ had a degradation rate constant 2.4–4.2 times greater than UV₂₅₄. This aligns with the MC-LR molar absorption (ε) and quantum yield (Φ) in deionized (DI) water. LC-HRMS revealed the photoisomer concentration increasing with UV dose. Trends of abundant photoisomers indicate further degradation. Together, these trends indicate UV₂₂₂ is a more complete pathway toward protein phosphatase inhibition 2A (PP2A) inactive compounds than UV₂₅₄. Electrical energy per order (E_EO) for UV₂₂₂ and UV₂₅₄ was similar across all water matrices and analytical methods, demonstrating that UV₂₂₂ has the potential to surpass the degradation and electrical efficiency of UV₂₅₄ used in water disinfection.