Global eutrophication of growth-limiting nutrients for plants and microbes, including nitrogen (N) and phosphorus (P), can cause enzymatic feedbacks at different levels of biological organization that in turn drive soil organic matter (SOM) decomposition. Because land management practices, such as fire in mesic grasslands, also impact nutrient availability, it is important to understand how soil feedbacks may manifest under multifactorial change. Here, using a thirty-year field experiment that crosses N- and P-fertilization (alone and in combination) with contrasting fire treatments (annual burning and fire suppression) in a tallgrass prairie ecosystem, we evaluated evidence for three possible feedbacks (product-inhibition, enrichment of fast-growing copiotrophic taxa, and soil pH shift) by measuring soil extracellular enzyme activities (EEAs) and microbial community composition (16S rRNA genes) monthly for a year. Consistent with product-inhibition feedback predictions, both N-fertilization and fire suppression (which increases soil N availability) decreased N-acquiring relative to C-acquiring EEAs, suggesting reduced N limitation. P-fertilization did not lower acid phosphatase activity, thus the product-inhibition feedback hypothesis was not supported under P eutrophication conditions. Although N- and P-fertilization, alone and in combination, did decrease putatively oligotrophic populations in favor of putatively copiotrophic populations, the hypothesized tradeoff for faster growth, a concomitant decrease in all soil EEAs, was only observed in unburned soils fertilized with N. Finally, observed changes in EEAs were not driven by acidification, in contrast to other fertilization experiments. Overall, results suggest that higher N availability affects enzymatic feedbacks primarily through product-inhibition, but a threshold-like growth tradeoff (copiotrophic) response is possible under the combination of fire suppression and N-fertilization. Inherent soil properties may modulate site-specific responses to fertilization, as evidenced by weak pH and EEA responses to N- and P-fertilization, respectively. Finally, soil microbial community change following chronic fertilization did not reliably predict the “copiotrophic” feedback of reduced SOM decomposition potential.