The reactivity of [Cr/Se/Te] multilayers under annealing was investigated using X-ray reflectometry, in situ X-ray diffraction, X-ray absorption fine structure (XAFS) measurements and transmission electron microscopy. For all samples, interdiffusion was complete at temperatures between 100 and 300°C, depending on the repeating tri-layer thickness. A crystalline phase nucleated approximately 20°C above the temperature where interdiffusion was finished. The first crystalline phase in a binary Cr/Te sample was layered CrTe3 nucleating at 230°C. In ternary samples (Se:Te=0.6–1.2), the low-temperature nucleation of such a layered CrQ3 (Q=Se, Te) phase is suppressed and instead the phase Cr2Q3 nucleates first. Interestingly, this phase decomposes around 500°C into layered CrQ3. In contrast, binary Cr/Se samples form stable amorphous alloys after interdiffusion and Cr3Se4 nucleates around 500°C as the only crystalline phase. Evaluation of the XAFS data of annealed samples yield Se–Cr distances of 2.568(1) and 2.552(1)Å for Cr2Q3 and CrQ3, respectively. In the latter sample, higher coordination shells around Se are seen accounting for the Se–Te contacts in the structure.