The unicellular green alga Chlamydomonas reinhardtii is a widely studied reference organism, particularly in photosynthesis research. It employs photoprotective mechanisms, such as state transitions (ST) and non‐photochemical quenching (NPQ), to cope with rapid light changes. Most widely used strains share a recent common ancestor yet differ by up to ~50 000 nuclear variants—genetic diversity that is often overlooked. Even among ‘wild type’ strains, we document significant phenotypic differences, such as pigment accumulation, and nutrient utilization. To elucidate the basis for this variation, we compared transcriptomes and physiological traits of seven commonly used laboratory strains, including the reference strain and the CLiP mutant library parental strain. Despite identical growth conditions, ~40% of genes were differentially expressed between strains. Most of these differences are attributable to changes that have accrued during laboratory propagation, and adverse conditions may have driven transcriptomic drift. At the physiological level, we catalog the range of strain‐dependent responses related to photosynthesis and high light (HL) acclimation. Specifically, (i) all strains develop NPQ upon HL exposure, but to various degrees, (ii) they show a substantial variation in ST capacity, and (iii) they regulate the composition of the photosynthetic apparatus differently. We find that NPQ levels do not correlate with LHCSR3 expression, suggesting an additional layer of NPQ regulation. STs are constantly activated and independent of growth light intensities. Overall, our findings highlight significant strain‐to‐strain differences in virtually all photosynthetic parameters, emphasizing the importance of careful strain selection in future research endeavors.