Strong correlations of O3-CH2O, O3-CO and CO-CH2O were observed during the Deriving Information on Surface Conditions from Column and Vertically Resolved Observations Relevant to Air Quality (DISCOVER-AQ) aircraft experiment in July 2011 over the Washington-Baltimore area. The linear regression slopes of observed O3-CH2O, O3-CO, and CO-CH2O do not vary significantly with time (11 a.m. to 4 p.m.) or altitude in the boundary layer. These observed relationships are simulated well by a regional chemical transport model. Using tagged-tracer simulations, we find that biogenic isoprene oxidation makes the largest contribution to the regression slope of O3-CH2O across much of the eastern United States, providing a good indicator for O3 enhanced by biogenic isoprene oxidation. In contrast, the regression slope of O3-CO is controlled by both anthropogenic and biogenic emissions. Therefore, we use the CO-CH2O relationship to separate biogenic from anthropogenic contributions to CO. By combining these regressions, we can track the contributions to surface O3 by anthropogenic and biogenic factors and build a fast-response ozone estimator using near-surface CH2O and CO concentrations as inputs. We examine the quality of O3 estimator by increasing or decreasing anthropogenic emissions by up to 50%. The estimated O3 distribution is in reasonably good agreement with the full-model simulations (R2 > 0.77 in the range of 30% to +50% of anthropogenic emissions). The analysis provides the basis for using high-quality geostationary satellites with UV, thermal infrared, or near-infrared instruments for observing CH2O and CO to improve surface O3 distribution monitoring. The estimation model can also be applied to derive observation-derived regional metrics to evaluate and improve full-fledged 3-D air quality models.