Lead (Pb) is one of the most common environmental pollutants. Lead has an acute toxic effect on soil biotas and the enzymatic system of soils. The objective of this study is to carry out enzymatic diagnostics of soil health in the European part of Russia after Pb contamination. As a part of the simulation experiment, Pb (at maximum permissible concentrations (MPCs) of 1, 10, and 100) was used to contaminate 12 types of soils in the south and center of the European part of Russia, which differed in their physical and chemical properties. To assess soil health, the activity of oxidoreductases (catalase, dehydrogenases, and cysteine reductase) and hydrolases (invertase, urease, and phosphatase) was studied. Most enzymes were inhibited with increased Pb dosage. The most sensitive soils to Pb contamination, assessed by enzyme activity, are soils of semi-deserts and dry steppes. Cysteine reductase is considered the most sensitive enzyme to Pb contamination. The most informative indicators for Pb contamination were phosphatase, cysteine reductase, and invertase. The P (phosphatase) cycle and the redox enzyme (catalase) also have instability in Pb-contaminated soils. The C (invertase and dehydrogenases) and N (urease) cycles do not change significantly when contaminated with lead. The results of this study can be used for the diagnostics of the condition of soils in different natural areas after Pb contamination.