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Giant saguaro (Carnegiea gigantea) is one of the longest-lived and massive cacti species in the Americas. They occur throughout the Sonoran Desert region with a distribution spanning a five-fold gradient in mean annual precipitation. Relationships between fitness traits, including stem growth, and spatio-temporal climate patterns are still poorly understood in saguaro, but are assumed to be largely coupled to summer precipitation. To better understand patterns of climate sensitivity in giant saguaro, annual stem growth, carbon isotope ratios (delta C-13) in spine tissues, and seasonal variation in stem volume, a proxy for stem water storage, were evaluated over a single growing season (2014) in six widely distributed populations in the northern Sonoran Desert, and over four consecutive growing seasons (2013-2016) in two populations with differences in mean annual precipitation and site moisture (M-i), defined as precipitation amount divided by mean atmospheric vapor pressure deficit. We hypothesized that saguaro growth and delta C-13 would be coupled to a complex suite of climate conditions that include winter precipitation and aridity. Annual stem growth of all populations was generally better correlated to M-i than precipitation alone and was best correlated with M-i measured over the hydrologic year, October 2013-September 2014 (F = 39.8, P < 0.0001). Likewise, mean delta C-13 increased with M-i, with the highest correlation with M-i calculated for July 2013-August 2014 (F = 38.4.0, P < 0.0001). Annual stem growth measured across all populations was well correlated to delta C-13 in spines produced during the current year of growth (F = 36.3, P < 0.0001). Annual variation in stem growth appeared to reflect annual variation in mean stem volume measured monthly from the summer of the previous year to the summer of the current year of growth. Results suggest that stem growth and photosynthetic physiology recorded by delta C-13 are coupled to a complex suite of climate conditions with a strong legacy effect from the previous summer and winter. These findings provide new insight on the effects of summer and winter drought and a warming climate on the photosynthesis, growth, and fitness of giant saguaro.