A combination of mechanical testing, EBSD and crystal plasticity finite element modeling were used to investigate the influence of temperature on the fragmentation of grains in a zirconium alloy. The results demonstrate that grains of Zircaloy-4 fragment more as the temperature rises. This trend can be explained by an increasing difference between the CRSS values for 〈c+a〉 slip and 〈a〉 slip as temperature rises. This change in relative slip activities with temperature is supported by experimental observations of macroscopic anisotropy and in-grain misorientation axes calculated from EBSD data, as well as plasticity modeling. By tracking the microstructural evolution during deformation, it is shown that the two major texture components fragment to different degrees under the action of prismatic slip. Grains in the $ \left〈 {11\overline{2} 0} \right〉 $ 112¯0 fiber are significantly more stable than those in the $ \left〈 {10\overline{1} 0} \right〉 $ 101¯0 fiber, which break up. Grains of the latter fiber fragment heterogeneously as portions of the grain rotate in opposite directions, and some do not rotate at all.