Reclaimed water is an important water resource to alleviate the agricultural water crisis around the world. Meanwhile, the environmental behavior of emerging contaminants and the impact on soil microorganisms during the reuse of recycled water have attracted wide attention. In this study, the content of trimethoprim and sulfamethoxazole in the 0–120 cm soil irrigated with reclaimed water increased by 42% and 61%, respectively, compared with the soil irrigated with groundwater water. Trimethoprim and sulfamethoxazole both showed a downward migration trend after 12 years of irrigation with reclaimed water. The reclaimed irrigation resulted in the peak concentration of trimethoprim and sulfamethoxazole at the depth of 0–120 cm soil increased to 2.3 and 1.8 times of the control, while no significant change on the concentration of triclosan in soil was found. The three types of pharmaceuticals and personal care products showed significant increase in the surface soil from 0 to 40 cm. The total bacterial abundance significantly increased by 16% after irrigation with reclaimed water, but there was no significant effect on the total archaea abundance (p > 0.05). The correlation results showed high negative associations between the rate of variation of soil pharmaceuticals and personal care products and the total number of bacteria (p < 0.05), in which the increase of soil pharmaceuticals and personal care products concentration under irrigation with reclaimed water would reduce the soil microbial abundance. This study will help us understand the fate of three chemical components in soil with long term irrigation with reclaimed water and their effects on soil microorganisms.