Oxygen saturation is a crucial indicator in the management of various diseases and in preoperative diagnosis, and the detection of oxygen content is valuable in guiding clinical treatment. However, as the classical and dominant oxygen detection strategies, current photoelectric oximeters and electrochemicalbased blood gas analyzers often suffer from significant interindividual variation and poor compliance, respectively. In recent years, wearable microneedles (MNs) for analyzing biomarkers in interstitial fluid (ISF) have received great attention and recognition mainly for the reason that the content of the substances distributed in ISF has a better correlation with that in blood circulation compared with other body fluids such as sweat and saliva. Herein, an MN-based electrochemical array system was developed for continuous subcutaneous oxygen sensing, in which goldmodified commercial acupuncture MNs were used as the sensing units, and a tailored mini-workstation, a nonwoven fabric, and a water and air isolation membrane were integrated to fabricate a wearable array patch. Notably, a multifunctional swelling resin with good biocompatibility was adopted to decorate the MN surface as a protective layer and as an electrolyte gel. The swelling resin featured the ability to reduce epidermis secretions during the sensor array penetrating the skin and to decrease the interference of other biomolecules in ISF for oxygen assay during measurement. This proposed array patch can perform the subcutaneous oxygen analysis in the physiological range of 6−150 mmHg with high sensitivity (0.3817 μA/mmHg) and low theoretical limit of detection (5.06 mmHg). It also showed decent stability and selectivity in the presence of several kinds of exogenous and endogenous substances. Finally, the patch accomplished continual monitoring of the subcutaneous oxygen content during long-term physical exercise, showing great potential in providing warning about the hypoxia status of the human body. It could be foreseen that this high-performance patch will play an active role in respiratory disease evaluation, surgical monitoring, and public health care.