This paper explores the various contributors to uncertainty on predictions of the antineutrino source term which is used for reactor antineutrino experiments and is proposed as a safeguard mechanism for future reactor installations. The errors introduced during simulation of the reactor burnup cycle from variation in nuclear reaction cross sections, operating power, and other factors are combined with those from experimental and predicted antineutrino yields, resulting from fissions, evaluated, and compared. The most significant contributor to uncertainty on the reactor antineutrino source term when the reactor was modeled in 3D fidelity with assembly-level heterogeneity was found to be the uncertainty on the antineutrino yields. Using the reactor simulation uncertainty data, the dedicated observation of a rigorously modeled small, fast reactor by a few-ton near-field detector was estimated to offer reduction of uncertainty on antineutrino yields in the 3.0–6.5 MeV range to a few percent for the primary power-producing fuel isotopes, even with zero prior knowledge of the yields.