Research was conducted to study the response and detoxification mechanisms of earthworms collected from Cd-contaminated areas in Hunan Province, South China. Metaphire californica, the dominant earthworm species in fields, referred as earthworm-A and -B that collected from low- (0.81 mg kg⁻¹) and high-Cd soil (13.3 mg kg⁻¹), respectively, for exchanging incubation in laboratory. The results showed that earthworm-A gradually accumulated higher Cd when exposed in the high-Cd soil, whereas Cd concentration of earthworm-B decreased after being transferred to low-Cd soil (albeit BAF_Cd >20). The integrated biomarker response index was calculated with the biomarkers of antioxidant systems (e.g., superoxide dismutase (SOD), peroxidase (POD), glutathione (GSH), glutathione peroxidase (GPx), glutathione-S transferase (GST), and malondialdehyde (MDA)) and energy index (e.g., protein and glycogen) in M. californica. GSH, GPx, and GST contributed the most to the integrated biomarker response (IBR) in earthworm-A when exposed in high-Cd soil for 14 d. Earthworm-B responded with higher GST and GPx activities and decreased protein content in low-Cd soil. For 28 d, the response of earthworm-A was not evident in either low- or high-Cd soil, and the inductive effect of metal stress on earthworm-B tended to be stable, except for the higher MDA content (p < 0.05) when exposed in low-Cd soil. The IBR index of earthworm-B (2.93 and 3.40) in low- and high-Cd soil, respectively, was higher than that of earthworm-A (0.89 and 1.0). Overall, earthworm-A exhibited a detoxification process to resist high-Cd toxicity from low-to high-Cd soil. Earthworm-B exhibited a physiological resilience once its habitat had changed to a normal or low-Cd soil environment, possibly owing to the cost of its resistance adaptation to the historical highly contaminated soil in fields.