The time variations in the Gutenberg–Richter b-value are minutely studied based on the data of highly accurate seismological observations at the Garm prognostic site, Tajikistan, where a stationary network of seismic stations of the Complex Seismological Expedition (CSE) of Schmidt Institute of Physics of the Earth (IPE) of the USSR (Russian) Academy of Sciences was in operation from 1955 to 1992. A total of 93035 local earthquakes ranging from 0.0 to 6.3 in the Ml magnitudes are considered. The spatiotemporal fluctuations in the minimal magnitude of completeness of the earthquakes, Mc, are analyzed. The study considers a 25-year interval of the observations at the center of the observation system within which Mc = 0.9. It is shown that in most cases, the b-value and log10E2/3 experience characteristic time variations before the earthquakes with magnitudes higher than the minimal magnitude of the predicted earthquake (MPE). The 6-year anomaly in the parameters’ b-value, log10E2/3, and log10N associated with the single strongest earthquake with M = 6.3 that occurred in the observation region on October 26, 1984 is revealed. The inversely proportional relationship is established between the time variations in the b-value and the time variations in the velocities of seismic waves Vp and Vp/Vs. It is shown that the exponent p in the power function which links the time variations of the b-value and log10E2/3 is higher in the zones of crustal compression than in the zones of extension. It is simultaneously confirmed that the average b-value in the zones of compression is lower than in the zones of extension. It is established that in the case of earthquakes with M ≥ 2.6, the time series of seismic activity log10Ni and the time series of the b-value are highly cross correlated with a coefficient of r ≈ 0.75, whereas in the case of earthquakes with M ≥ 0.9, the coefficient of cross correlation between these time series is close to zero (r ≈ 0.06). The law of variations in the slope of the lines approximating the relationship between the log10Ni time series in the different magnitude ranges (M ≥ Mci) and b-value time series is obtained. It is hypothesized that the seismic activity of the earthquakes with high magnitudes can be estimated provided that the parameters of the time series of the b-value and time series of the number of earthquakes logN(ΔMi) in the range of low magnitudes are known. It is concluded that using the parameter log10N for prognostic estimates of the strong earthquakes only makes sense for earthquakes having moderate and large magnitudes. It is inferred that the time variations in the b-value are predominantly contributed by the time variations of the earthquakes with relatively large magnitudes.