Inorganic-organic hybrid materials represent a large share of newly reported structures, owing to their simple synthetic routes and customizable properties¹. This proliferation has led to a characterization bottleneck: many hybrid materials are obligate microcrystals with low symmetry and severe radiation sensitivity, interfering with the standard techniques of single-crystal X-ray diffraction^2,3 and electron microdiffraction^4-11. Here we demonstrate small-molecule serial femtosecond X-ray crystallography (smSFX) for the determination of material crystal structures from microcrystals. We subjected microcrystalline suspensions to X-ray free-electron laser radiation^12,13 and obtained thousands of randomly oriented diffraction patterns. We determined unit cells by aggregating spot-finding results into high-resolution powder diffractograms. After indexing the sparse serial patterns by a graph theory approach¹⁴, the resulting datasets can be solved and refined using standard tools for single-crystal diffraction data^15-17. We describe the ab initio structure solutions of mithrene (AgSePh)^18-20, thiorene (AgSPh) and tethrene (AgTePh), of which the latter two were previously unknown structures. In thiorene, we identify a geometric change in the silver-silver bonding network that is linked to its divergent optoelectronic properties²⁰. We demonstrate that smSFX can be applied as a general technique for structure determination of beam-sensitive microcrystalline materials at near-ambient temperature and pressure.