Lake Arrowhead, an oligotrophic alpine lake in southern California, experienced a drought period from summer 2012 to winter 2018 followed by a season of intense storms in winter 2019 resulting in lake flooding. This study investigates the effects of seasonal variations combined with 3.5 m water level fluctuation from May 2018 to April 2019, on water quality and hydrodynamics of Lake Arrowhead. In-situ measured meteorological data and water quality profiles in five different bays were used to develop and calibrate a three-dimensional lake hydrodynamic model. The mean relative errors between simulated and measured temperature and salinity profiles were 6.1% and 4.2%, respectively. Root mean square errors between the measured and simulated water temperatures were slightly larger during the stratified period. However, no specific pattern was observed in error analysis of salinity simulations.Strong thermal stratification during summer and early-fall resulted in hypoxic hypolimnetic waters with dissolved oxygen (DO) concentrations of <1 mg L−1. Turbulent kinetic energy (TKE) generated by convective motions in the water column due to surface heat loss was typically more than two times greater than the wind-induced mixing energy during the stratification period. The lake experienced an energetic turbulent mixing regime with TKE fluxes >1.5 m−3 s−3, and Lake numbers <0.1 during the winter cooling period, resulting in a complete water column turnover and resuspension of bottom sediments. Entrainment of the hypoxic hypolimnion layers and sediment resuspension resulted in decreased DO and pH in the water column from December 2018 through mid-January 2019. Comparisons of Wedderburn and Lake numbers during different stratification conditions indicated the same trends in the strong stratification period (square of buoyancy frequency >10−4 s−2). However, in other conditions, the Lake number, considering the lake bathymetry and density profile, could better reflect vertical mixing conditions.