According to the data sets of fine particulate matter (PM2.5) and its components in 35 cities in the Huaihe River Basin from 2015 to 2021, the temporal and spatial distribution patterns of pollutants were analyzed. The influence of meteorological factors on PM2.5 concentrations was examined using a random forest model. The original series of PM2.5, sulfate (SO42-), nitrate (NO3-), ammonium salt (NH4+), organic matter (OM), and black carbon (BC) were rebuilt using KZ (Kolmogorov-Zurbenko) filtering and multiple linear regression (MLR) to quantify the effects of meteorological conditions. The results demonstrated that from 2015 to 2021, the declining rates of PM2.5, SO42-, NO3-, NH4+, OM, and BC in the Huaihe River Basin were 4.71, 0.99, 1.05, 0.77, 1.01, and 0.19 μg·(m3·a)-1, respectively. The high mass concentrations of PM2.5 and its components were concentrated in the central and western regions of the HRB, whereas those in coastal and southern cities were lower. The variance contributions of the short-term, seasonal, and long-term components of PM2.5 to the original PM2.5 sequences in 35 cities were 51.6%, 35.9%, and 7.0%, respectively. The PM2.5 in coastal cities were more affected by the short-term components. The meteorological conditions were unfavorable for PM2.5 reduction in the HRB from 2015 to 2018, whereas the meteorological conditions supported the PM2.5 decrease from 2019 to 2021. From 2015 to 2021, the contribution rates of meteorological conditions to the long-term component reductions of PM2.5, SO42-, NO3-, NH4+, OM, and BC were 28.3%, 29.1%, 31.0%, 29.3%, 27.8%, and 28.6%, respectively. The contribution rates of meteorological conditions to the long-term PM2.5 reduction were 43.4%, 25.6%, 25.5%, and 20.6% in the HRB cities in Anhui, Shandong, Jiangsu, and Henan Provinces, respectively. With the decrease in PM2.5 concentration in the HRB, the sulfur oxidation rate (SOR) increased significantly, while the nitrogen oxide oxidation rate (NOR) changed little.