Cover crops (CC) improve soil quality, including soil microbial enzymatic activities and soil chemical parameters. Scientific studies conducted in research centers have shown positive effects of CC on soil enzymatic activities; however, studies conducted in farmer fields are lacking in the literature. The objective of this study was to quantify CC effects on soil microbial enzymatic activities (β-glucosidase, β-glucosaminidase, fluorescein diacetate hydrolase, and dehydrogenase) under a corn (Zea mays L.)–soybean (Glycine max (L.) Merr.) rotation. The study was conducted in 2016 and 2018 in Chariton County, Missouri, where CC were first established in 2012. All tested soil enzyme levels were significantly different between 2016 and 2018, irrespective of CC and no cover crop (NCC) treatments. In CC treatment, β-glucosaminidase activity was significantly greater at 0–10 cm depth in 2016 and at 10–20 and 20–30 cm in 2018. In contrast, dehydrogenase activity was significantly greater in NCC in 2018. Soil pH and organic matter (OM) content were found to be significantly greater in CC. Overall, CC have mixed effects on soil enzyme activities and positive effects on soil OM compared to NCC. This study highlights the short-term influence of CC and illustrates the high spatial and temporal variability of soil enzymes under farmer-managed fields.