AbstractA novel virus, tilapia lake virus (TiLV), has been identified as a key pathogen responsible for disease outbreak and mass mortality of farmed tilapia. We used a deterministic susceptible‐infectious‐mortality (SIM) model to derive key disease information appraised with published TiLV‐induced cumulative mortality data. The relationship between tilapia mortality and TiLVexposure dosages was described by the Hill model. Furthermore, a disease control model was proposed to determine the status of controlled TiLVinfection using a parsimonious control reproduction number (RC)‐control line criterion. Results showed that the key disease determinants of transmission rate and basic reproduction number (R0) could be derived. The medianR0estimate was 2.59 in a cohabitation setting with 2.6 × 105 TCID50 fish−1TiLV. The presentRC‐control model can be employed to determine whether TiLVcontainment is feasible in an outbreak farm by quantifying the current level of transmission. TheSIMmodel can then be applied to predict what additional control is required to manageRC < 1. We offer valuable tools for aquaculture engineers and public health scientists the mechanistic‐based assessment that allows a more rigorous evaluation of different control strategies to reduce waterborne diseases in aquaculture farming systems.