Alchemical binding free energy (BFE) calculations offer an efficient and thermodynamically rigorous approach to in silico binding affinity predictions. As a result of decades of methodological improvements and recent advances in computer technology, alchemical BFE calculations are now widely used in drug discovery research. They help guide the prioritization of candidate drug molecules by predicting their binding affinities for a biomolecular target of interest (and potentially selectivity against undesirable antitargets). Statistical variance associated with such calculations, however, may undermine the reliability of their predictions, introducing uncertainty both in ranking candidate molecules and in benchmarking their predictive accuracy. Here, we present a computational method that substantially improves the statistical precision in BFE calculations for a set of ligands binding to a common receptor by dynamically allocating computational resources to different BFE calculations according to an optimality objective established in a previous work from our group and extended in this work. Our method, termed Network Binding Free Energy (NetBFE), performs adaptive BFE calculations in iterations, re-optimizing the allocations in each iteration based on the statistical variances estimated from previous iterations. Using examples of NetBFE calculations for protein binding of congeneric ligand series, we demonstrate that NetBFE approaches the optimal allocation in a small number (≤5) of iterations and that NetBFE reduces the statistical variance in the BFE estimates by approximately a factor of 2 when compared to a previously published and widely used allocation method at the same total computational cost.