In the next decades, the astrobiological community will debate whether the first observations of oxygen in an exoplanet$$s atmosphere signifies life, so it is critical to establish procedures now for collection and interpretation of such data. We present a step-by-step observational strategy for using oxygen as a robust biosignature, to prioritize exoplanet targets and design future observations. It is premised on avoiding planets lacking subaerial weathering of continents, which would imply geochemical cycles drastically different from Earth$$s, precluding use of oxygen as a biosignature. The strategy starts with the most readily obtained data: semi-major axis and stellar luminosity to ensure residence in the habitable zone; stellar XUV flux, to ensure an exoplanet can retain a secondary (outgassed) atmosphere. Next, high-precision mass and radius information should be combined with high-precision stellar abundance data, to constrain the exoplanet$$s water content; those incompatible with less than 0.1 wt % H$_{2}$O can be deprioritized. Then, reflectance photometry or low-resolution transmission spectroscopy should confirm an optically thin atmosphere. Subsequent long-duration, high-resolution transmission spectroscopy should search for oxygen and ensure that water vapor and CO$_{2}$ are present only at low (10$^{2}$-10$^{4}$ ppm levels). Assuming oxygen is found, attribution to life requires the difficult acquisition of a detailed, multispectral light curve of the exoplanet to ensure both surface land and water. Exoplanets failing some of these steps might be habitable, even have observable biogenic oxygen, but should be deprioritized because oxygen could not be attributed unambiguously to life. We show how this is the case for the Solar System, the 55 Cnc System, and the TRAPPIST-1 System, in which only the Earth and TRAPPIST-1e successfully pass through our procedure.
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