Bubble-plume mixing systems are often deployed in eutrophic lakes and reservoirs to manage phytoplankton taxa. Unfortunately, inconsistent outcomes from bubble-plume (induced) mixing are often reported in the literature. The present study investigates the response of phytoplankton to induced mixing using a whole-reservoir field experiment and a three-dimensional hydrodynamic model (Si3D) coupled with the Aquatic EcoDynamics (AED) model through the framework for aquatic biogeochemical modelling (FABM). The coupled Si3D-AED model is validated against a 24-h field mixing experiment and subsequently used for a numerical parametric study to investigate phytoplankton responses to various induced mixing scenarios in which the phytoplankton settling rate, phytoplankton growth rate, reservoir depth, and mixing system diffuser depth were sequentially varied. Field observations during the mixing experiment suggest that the total phytoplankton concentration (measured in across the reservoir was reduced by nearly 10% during the 24-h mixing period. The numerical modeling results show that phytoplankton concentration may be substantially affected by the functional traits of the phytoplankton and the deployment depth of the mixing diffuser. Interestingly, the numerical results indicate that the phytoplankton concentration is controlled by reduced growth rates due to light limitation in deep reservoirs (>20 m), whereas settling loss is a more important factor in shallow reservoirs during the mixing period. In addition, the coupled Si3D-AED model results suggest that deploying the mixing diffuser deeper in the water column to increase mixing depth may generally improve the successful management of cyanobacteria using bubble-plume mixing systems. Thus, the coupled Si3D-AED model introduced in the present study can assist with the design and operation of bubble-plume mixing systems.