Fertilization increases productivity in Eucalyptus plantations, but losses in productivity associated with soil fertility continue at operational scales. In this study, we evaluated the fertilization response (FR), light use efficiency (LUE) and growth efficiency (GE), i.e., the amount of wood biomass accumulated per unit of light absorbed (LUE) and per unit of leaf area index of Eucalyptus plantations. We used a “twin plot” approach, with 161 blocks representing 52,700 ha of planted forests that spanned a broad range of edaphoclimatic conditions in southeastern Brazil. The normal plots (NP) were part of a permanent inventory network, whereas the twin plots (TP) received extra high levels of fertilization and extra weed control after fertilization. The intensive management (twin plots) led to a large increase of 5.3 Mg·ha−1·year−1 of wood increment. The region without dry periods and with soils with high clay content was most responsive to fertilization, with a 15% increment in the LUE and 10% increase in the GE of the TPs compared with those of the NPs. Our results suggested that water availability was the primary element affecting productivity and potential response to fertilization. With this information, decisions can be made on which regions should receive priority fertilization investments. However, more research is required to determine the most limiting nutrient in each type of environment.