The previous work (Huang and Li, Compos. Part B, 2015) proposed the failure mechanism in syntactic foams with low and high hollow microsphere volume fractions, based on the finite element simulation of localized stresses in the foam. In this work, in situ X‐ray microtomography of uniaxial compression tests was performed to provide the direct experimental evidence to the proposed mechanism by tracking the internal three‐dimensional failure process in epoxy syntactic foams with different cenosphere volume fractions (V). It was found that for both the low and high V, microcracks initiate in the matrix in the top and bottom of crushed cenospheres where the tensile stress concentrates, and then propagate longitudinally to become macrocracks. Increasing the cenosphere volume fraction also leads to the formation of matrix microcracks in the connection zone where the stress concentrates significantly; the matrix microcracks thus propagate diagonally and longitudinally in the high V foam. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47491.