Certain trees in semi-arid environments are surpassing their physiological thresholds because of erratic rainfall and rising global temperatures. Mistletoes (Loranthaceae) may also be making large trees more susceptible to the physiological stress imposed by climate change. Therefore, we examined intraspecific variations of selected leaf traits of the mistletoe, Erianthemum dregei, and Sclerocarya birrea host trees along a rainfall gradient at three levels of mistletoe infection. We measured seven leaf traits across five mistletoe-host pairs at low, medium, and high rainfall sites. Rainfall had significant effects on all measured traits, except host leaf succulence. Hosts were more resource-acquisitive at intermediate rainfall, but more conservative at high rainfall. The reverse is true for mistletoes. Mistletoe infection only had an effect on host leaf area, specific leaf area, and stomatal conductance, but most mistletoe leaf traits were significantly influenced by infection intensity. Uninfected hosts were more resource-conservative, but highly infected hosts were resource-acquisitive. Conversely, mistletoes on low-infected hosts were associated with high resource acquisition, while those on high-infection trees were resource-conservative. Therefore, the antagonistic response of host trees and mistletoes to infection and rainfall suggests the potential for resilience to environmental change.