The impacts of urbanization, such as urban heat island (UHI) and nutrient loads, can influence tree function through altered physiology and metabolism and stress response, which has implications for urban forest health in cities across the world. Our goal was to compare growth-stimulating and stress-mitigating acclimation patterns of red maple (Acer rubrum) trees in deciduous forests embedded in a small (Newark, DE, US) and a large (Philadelphia, PA, US) city. The study was conducted in a long-term urban forest network on seventy-nine mature red maple trees spanning ten forests across Newark and Philadelphia. We hypothesized that red maples in Philadelphia forests compared to Newark forests will be healthier and more acclimated to warmer temperatures, elevated CO2 concentrations and reactive nitrogen (Nr) deposition, and higher nutrient/heavy metal loads. Therefore, these red maples will have higher foliar pigments, nutrients, and stress-indicating elements, enriched δ15N isotopes and increased free polyamines and amino acids to support a growth-stimulating and stress-induced response to urbanization. Our results indicate red maples are potentially growth-stimulated and stress-acclimated in Philadelphia forests experiencing a greater magnitude of urban intensity. Red maples in Philadelphia forests contained higher concentrations of foliar chlorophyll, %N, δ15N, and nutrients than those in Newark forests. Similarly, lower foliar magnesium and manganese, and higher foliar zinc, cadmium, lead, and aluminum reflected the difference in soil biogeochemistry in Philadelphia forests. Accumulation patterns of foliar free amino acids, polyamines, phosphorous, and potassium ions in red maples in Philadelphia forests shows a reallocation in cellular metabolism and nutrient uptake pathways responsible for physiological acclimation. Our results suggest the approach used here can serve as a model for investigating 'plant physiology' and the use of urban trees as a biomonitor of the impacts of 'urban pollution' on urban forests. The results suggest that cellular oxidative stress in trees caused by pollutant uptake is mitigated by the accumulation of free amino acids, polyamines, and nutrients in a larger city. Our study provides a framework for determining whether trees respond to complex urban environments through stress memory and/or acclimation.