Significant seasonal changes in chemical and microbiological water quality can occur in buildings at different fixture locations due to temperature and time dependent reaction rates. Here, a series of calibrated plumbing hydraulic‐water quality models were developed for the extensively monitored Retrofitted Net‐zero Energy, Water & Waste (ReNEWW) house in West Lafayette, Indiana, USA. The eight new models predict the absolute level of free chlorine, total trihalomethanes, copper, iron, lead, NO3− (nitrate‐nitrogen), heterotrophic plate count (HPC), and Legionella spp. concentration at each fixture for plumbing use, operational characteristics, and design layouts of the plumbing system. Model development revealed that the carrying capacity to describe Legionella spp. growth (and other organisms) under water usage and plumbing design conditions is lacking in the literature. Reducing simulated building water use by 25% prompted increased absolute concentrations of HPC and Legionella spp., each increasing by a factor of about 105. When the simulated service line length was increased, Legionella spp. concentrations increased by up to 106 gene copies /L in the Summer season. The proposed modeling framework can be used to support better planning, design, analysis, and operational decision‐making.