Limited information is available on the genetic variation and control for plant growth response to elevated CO2 (e[CO2]). Such information is necessary to understand plant adaptation and evolution in future rising CO2. Here, quantitative trait loci (QTL) for leaf growth, development, quality and leaf senescence were determined in a tree pedigree – an F2 hybrid of Populus trichocarpa T. & G and Populus deltoides Marsh, following season-long exposure to either current day ambient carbon dioxide (a[CO2]) or e[CO2] at 600 µL L−1. Leaf growth and development differed between the grandparents such that P. trichocarpa showed greater response to e[CO2]. In the F2 generation, leaf development and quality traits including leaf area, leaf shape, epidermal cell area, and stomatal number, specific leaf area (SLA), and the phenology trait, canopy senescence index, were sensitive to e[CO2]. Sixty-nine QTL were mapped for the 19 traits of plants in a[CO2] while 60 QTL were mapped for plants in e[CO2]. The results suggest that although many QTL mapped to common positions in a[CO2] and e[CO2], confirming their importance in determining growth, there was also differential genetic control for a number of traits including leaf senescence. Candidate genes were shown to collocate to regions where response QTL mapped. This study is the first to identify candidate genes that may be important in determining plant adaptation to future high-CO2 world.