Read-across enables the interpolation of a property for a target chemical from respective experimental data of sufficiently similar compounds. Employing a set of 692 organic compounds with experimental values for the 96 h fish toxicity toward the fathead minnow in terms of LC₅₀ (lethal concentration 50%) values, a read-across method has been developed that is based on atom-centered fragments (ACFs) for evaluating chemical similarity. Prediction of log LC₅₀ proceeds through reading across the toxicity enhancement over predicted narcosis-level toxicity in terms of the respective logarithmic ratio, log T_e, and adding the respective baseline narcosis LC₅₀ estimated from log K_ow (octanol/water partition coefficient). Depending on the minimum similarity imposed on a compound to serve as read-across basis for the target chemical, three different standard settings have been introduced, allowing one to perform screening-level estimations as well as predictions with intermediate and good confidence. The respective squared correlation coefficients (r²) are 0.73, 0.78, and 0.87, with root-mean square errors (rms) of 0.73, 0.60, and 0.39 log units, respectively. As a general trend, increasing the ACF minimum similarity increases the prediction quality at the cost of decreasing the application range. The method has the potential to assist in the predictive evaluation of fish toxicity for regulatory purposes such as under the REACH legislation.