Saponins form a group of plant-produced glycosides with potential as biopesticide ingredients. The environmental fate of saponins has never been fully investigated. In the present study, we use QS-18, a specific saponin from Quillaja saponaria as an example, to quantify hydrolysis under different conditions of pH, temperature and water chemical composition. Saponin hydrolysis in buffer solutions was base-catalyzed and followed first-order kinetics. Thus, hydrolysis was slow at pH 5.1 with a half-life of 330 ± 220 d (26 °C), which increases to 0.06 ± 0.01 d at pH 10.0. Hydrolysis rates were highly sensitive to temperature with an activation energy of 56.9 ± 14.2 kJ mol⁻¹ at pH 7.2. In strong contrast, hydrolysis in lake waters (pH 6.4–8.2) produced different patterns with a fast initial dissipation of 25 to 60% of the added saponin within the first five hours, followed by an extremely slow reaction with 25 to 75% unreacted saponin left after reaction times longer than 120 h. The fast dissipation followed by slow hydrolysis in lake water was hypothesized to be attributed to sorption and/or flocculation of saponins by inorganic nanoparticles and/or solutes in the lake water followed by inactivation of hydrolysis due to the sorption/flocculation. The present study demonstrates that saponins may hydrolyze slowly under acidic and cold conditions. In addition, it demonstrates that dissipation kinetics in natural waters may deviate substantially from the kinetics predicted based on laboratory experiments with “clean” buffered solutions. This emphasizes the need for a deeper understanding of the processes affecting the dissipation kinetics of potential toxins under natural conditions, as fate models based on laboratory derived kinetic data may be seriously flawed.