ZnO-CuO mesocrystal was prepared via topotactic transformation using one-step direct annealing of aqueous precursor solution and assembled into a H2S sensor. The ZnO-CuO mesocrystal-based sensor possesses good linearity and high sensitivity in the low-concentration range (10-200 ppb). Compared to pure CuO, the as-prepared ZnO-CuO mesocrystal sensor exhibited superior H2S sensing performance with a response ranging from 8.6 to 152 % towards H2S concentrations from 10 ppb to 10 ppm when applied at the optimized working temperature of 125 degrees C. The sensor showed excellent repeatability and good selectivity towards H2S gas even at a concentration four orders of magnitude lower than the interfering gases, such as H-2, CO2, CO, NO2, acetone, and NH3. The improved sensitivity could be attributed partially to the effective diffusion of analyte gas through the mesocrystal surface and the abundant accessible active sites. Moreover, the nanoscale p-n junctions within the mesocrystal, which could effectively manipulate the local charge carrier concentration, are also beneficial to boost the sensing performance.