The proliferation of coral reef organisms, such as the key ecological engineers and carbonate producers’ large benthic foraminifera (LBF), greatly relies on the mutual association with photosymbiotic algae. With respect to global change impacts such as ocean warming, evaluating stress and acclimatization responses is highly important, but probing proteins and partitioning host and symbionts are major obstacles for studying LBF. We therefore applied a label-free quantitative proteomics approach to LBF holobionts in order to detect changes in the relative abundances of proteins in response to different thermal-stress scenarios. Subsequent identification allowed for the partial assignment of 1,618 proteins to either foraminiferal host or endosymbiotic diatoms. While single and episodic thermal-stress events only induced minor metabolic impacts, chronic thermal stress diminished photosynthesis-related proteins among the symbionts. Stress response and proteolysis-related proteins increased in abundance, illustrating the extent of damage. In contrast to the symbionts, host homeostasis was maintained through extensive repair mechanisms and high protein turnover. Metabolic pathways were adjusted to the symbiont loss by using alternative energy resources. However, linking proteome to physiological data revealed that resource redistribution impairs growth and certainly other functions that could disturb carbonate production. We show how compartment partitioning can give insights into interactions and stress response mechanisms in photosymbiotic reef-calcifiers.