Brushite (CaHPO4.2H2O) is an important calcium phosphate encountered in bone tissue engineering and bone cement formulation. There are many studies on the synthesis and characterization of brushite, but full-scale substitution and replacement of Ca by Sr in brushite as a key element in medical and environmental applications has not yet been explored systematically. Therefore, this study aims to evaluate the effects of substitution of Ca by Sr on the microstructural and thermal properties of brushite, including the chemical phases present, crystallization, structural water and phase stability. The chemical phases were determined by means of powder X-ray diffraction. The thermal properties were studied by thermogravimetric analysis. Crystallization and surface morphology were analysed using scanning electron microscopy. Various properties were dependent on the incorporated Sr ions. The replacement percentage of Sr may be divided into two major stages: the first from 0% to 50%; and the second from 50% up to 100%. The (CaxSr1–x)HPO4.nH2O shows that micro-scale crystals of platy brushite formed in the first stage of Sr replacement, from 0% up to 50%. As Sr might inhibit the formation of crystals, crystal nucleation rates were reduced as the Sr percentage increased. An amorphous product formed as a result of 50% Sr replacement. The second stage of Sr replacement with Sr contents >50% yielded a new crystal morphology corresponding mainly to SrHPO4.nH2O. The complete replacement of Ca by Sr transforms the brushite with platy microcrystals into SrHPO4 nanosheets.