We examine the impact of changes in ozone (O3), particulate matter (PM2.5), temperature, and humidity on the health of vegetation in dense urban environments, using a very high-resolution, ground-based Visible and Near-Infrared (VNIR, 0.4–1.0 μm with a spectral resolution of 0.75 nm) hyperspectral camera deployed by the Urban Observatory (UO) in New York City. Images were captured at 15 min intervals from 08h00 to 18h00 for 30 days between 3 May and 6 June 2016 with each image containing a mix of dense built structures, sky, and vegetation. Vegetation pixels were identified using unsupervised k-means clustering of the pixel spectra and the time dependence of the reflection spectrum of a patch of vegetation at roughly 1 km from the sensor that was measured across the study period. To avoid illumination and atmospheric variability, we introduce a method that measures the ratio of vegetation pixel spectra to the spectrum of a nearby building surface at each time step relative to that ratio at a fixed time. This “Compound Ratio” exploits the (assumed) static nature of the building reflectance to isolate the variability of vegetation reflectance. Two approaches are used to quantify the health of vegetation at each time step: (a) a solar-induced fluorescence indicator (SIFi) calculated as the simple ratio of the amplitude of the Compound Ratio at 0.75 μm and 0.9 μm, and (b) Principal Component Analysis (PCA) decomposition designed to capture more global spectral features. The time dependence of these vegetation health indicators is compared to that of O3, PM2.5, temperature, and humidity values from a distributed and publicly available in situ air quality sensor network. Assuming a linear relationship between vegetation health indicators and air quality indicators, we find that changes in both SIF indicator values and PC amplitudes show a strong correlation (r2 value of 40% and 47%, respectively) with changes in air quality, especially in comparison with nearby buildings used as controls (r2 value of 1% and 4%, respectively, and with all molecular correlations consistent with zero to within 3σ uncertainty). Using the SIF indicator, O3 and temperature exhibit a positive correlation with changes in photosynthetic rate in vegetation, while PM2.5 and humidity exhibit a negative correlation. We estimate full covariant uncertainties on the coefficients using a Markov Chain Monte Carlo (MCMC) approach and demonstrate that these correlations remain statistically significant even when controlling for the effects of diurnal sun-sensor geometry and temperature variability. This work highlights the importance of quantifying the effects of various air quality parameters on vegetation health in urban environments in order to uncover the complexity, covariance, and interdependence of the numerous factors involved.