Recent experimental studies have detected the presence of anoxic microzones in hyporheic sediments. These microzones are small‐scale anoxic pores, embedded within oxygen‐rich porous media and can act as anaerobic reaction sites producing reduction compounds such as nitrous oxide, a potent greenhouse gas. Microbes are a key control on nutrient transformation in hyporheic sediment, but their associated biomass growth is also capable of altering hydraulic flux, leading to potential bioclogging. Here, we developed one of the first computational modeling approaches that combined hydraulics and microbial conditions to explore the continuous evolution of microzones in stream sediments. The model assessed stream and sediment conditions with different hydraulic flux (0.1–1.0 m/day Darcy flux), nutrient concentrations (O₂ = 8 mg/L, OrgC = 20 mg/L, NO⁻₃ = 1.5–3 mg/L, and NH₃ = 0.5–1 mg/L), and biomass scenarios (with and without). The model domain is a pore network model with random sized pore‐throat radii creating heterogeneous and anisotropic flow that is representative of a natural streambed composed of medium sand with a hydraulic conductivity of 0.8 m/day. Results from 30 day simulations indicate that hyporheic microzone formation will occur and microzone distributions are not simply controlled by residence time alone, rather by the complex interactions of hydraulic flux, nutrient concentrations, and biomass, with bioclogging having strong feedbacks on both hydraulics and nutrients. Under all conditions with biomass growth, anoxic microzones were unstable, perishing a few days after formation, because bioclogging primarily occurs near the influent (downwelling) area of the hyporheic zone. In turn, this bioclogging shifts transport conditions from advection‐dominated to diffusion‐dominated transport, removing all oxic regions in the hyporheic zone. Overall, results from the modeling show that anoxic microzones are likely to form under many hyporheic zone conditions, and be dynamic through space and time as they are dependent on both hydraulic flux and nutrient transport.