Soil microbes and enzymes in permafrost peatland are sensitive to temperature changes, which might result in more potential loss of carbon and increase in available nitrogen from permafrost peatlands in a warming world. We previously demonstrated that 3-year warming could affect soil microbial abundance and enzymatic activity. However, soil microbial abundance and enzymatic activity in permafrost peatlands under long-term climate warming is not well understood. Therefore, a 6-year field manipulation experiment was used to assess the impact of long-term warming on soil microbial abundance and enzymatic activity in a permafrost peatland in northeastern China. Results showed that 6-year warming increased the abundance of bacteria in 0 to 15 cm soil under tussock and from shrub rhizosphere, fungi from shrub non-rhizosphere, and archaea under tussock and from the rhizosphere of shrub. These increased microbial abundances could stimulate soil carbon cycling and accelerate soil carbon loss in permafrost peatland under warming. Six-year warming increased methanogen abundance in 0 to 15 cm soil and methanotroph abundance in 15 to 30 cm soil under tussock, indicating that warming could enhance CH4 cycling. Soil nirS-denitrifier abundance from the 0 to 15 cm shrub rhizosphere increased under warming, thereby suggesting that warming stimulated denitrification and N2O emission. β-Glucosidase activity in 0 to 15 cm soil under tussock and from shrub rhizosphere increased, but invertase activity in 15 to 30 cm soil under tussock and from shrub rhizosphere showed opposite tendency under warming. DOC content tended to increase in the 0 to 15 cm rhizosphere soil, but decreased in shrub non-rhizosphere soil. Warming increased NH4+–N content in both rhizosphere and non-rhizosphere soil. Positive correlations between abundances of bacteria, archaea, contents of DOC, and NH4+–N in 0 to 15 cm soil suggest that increases in bacterial and archaeal abundance could indicate higher carbon and nitrogen availability in topsoil of permafrost peatlands under warming. The results offer new insights into the response of plant–soil-microbe interactions in permafrost peatlands to climate change.