Agronomic practices such as crop residue return and additional nutrient supply are recommended to increase soil organic carbon (SOC) in arable farmlands. However, changes in the priming effect (PE) on native SOC mineralization in response to integrated inputs of residue and nutrients are not fully known. This knowledge gap along with a lack of understanding of microbial mechanisms hinders the ability to constrain models and to reduce the uncertainty to predict carbon (C) sequestration potential. Using a 13C‐labeled wheat residue, this 126‐day incubation study examined the dominant microbial mechanisms that underpin the PE response to inputs of wheat residue and nutrients (nitrogen, phosphorus and sulfur) in two contrasting soils. The residue input caused positive PE through “co‐metabolism,” supported by increased microbial biomass, C and nitrogen (N) extracellular enzyme activities (EEAs), and gene abundance of certain microbial taxa (Eubacteria, β‐Proteobacteria, Acidobacteria, and Fungi). The residue input could have induced nutrient limitation, causing an increase in the PE via “microbial nutrient mining” of native soil organic matter, as suggested by the low C‐to‐nutrient stoichiometry of EEAs. At the high residue, exogenous nutrient supply (cf. no‐nutrient) initially decreased positive PE by alleviating nutrient mining, which was supported by the low gene abundance of Eubacteria and Fungi. However, after an initial decrease in PE at the high residue with nutrients, the PE increased to the same magnitude as without nutrients over time. This suggests the dominance of “microbial stoichiometry decomposition,” supported by higher microbial biomass and EEAs, while Eubacteria and Fungi increased over time, at the high residue with nutrients cf. no‐nutrient in both soils. Our study provides novel evidence that different microbial mechanisms operate simultaneously depending on organic C and nutrient availability in a residue‐amended soil. Our results have consequences for SOC modeling and integrated nutrient management employed to increase SOC in arable farmlands. This study examined the dynamics of priming effect (PE), controlled by the interaction of crop residue input and balanced supply of nutrients (N, P, and S), and the underlying mechanisms in relation to microbial community growth and extracellular enzyme activity. The results showed that the “microbial nutrient mining” and “microbial stoichiometry decomposition” mechanisms relating to nutrient availability mainly operated at high residue input. The image presents a conceptualized model based on key findings on the dominant occurrence of microbial mechanisms relating to PE, with implications to underpin soil organic carbon (SOC) modeling and guide integrated residue–nutrient management in croplands for SOC sequestration.