In order to investigate the seismic velocity structure in the region of concentrated severe damage during the 2016 Kumamoto earthquake sequence, we conducted continuous seismic observations in the central area of Mashiki Town, Kumamoto Prefecture. During 4 days of observations at eight temporary sites, 2 months after the mainshock, recordings from 30 aftershocks (1.7 ≤ Mj ≤ 4.3, 1.9 km ≤ depth ≤ 13.5 km) were obtained. The aftershock data showed that site amplifications at approximately 1 Hz are dominant in a zone where almost no buildings were damaged along the Akitsu riverside, whereas site amplifications at higher than 3 Hz are observed in the heavily damaged zones. Our data also showed that the peak acceleration and velocity amplitudes, as well as seismic intensities for the small events in the less damaged zone, are clearly larger than those in the damaged zones, implying that the damage distribution is inconsistent with site response based on linear site amplifications. The estimated phase velocities of Rayleigh waves using the aftershock and microtremor data show dispersive characteristics in the lower frequency range (0.26 ≤ f ≤ 1.27 Hz), but the values are substantially smaller than those derived from the P–S logging model at the nearest KiK-net strong-motion observation station KMMH16. The derived microtremor horizontal-to-vertical spectral ratios and earthquake radial-to-vertical (R/V) spectral ratios show common distinct peaks at around 0.4 Hz, which are possibly related to the response of deep sedimentary layers beneath the area. The refined velocity structure model that better accounts for both the phase velocity and common dominant peak indicates that the values of S wave velocity (Vs) above the bedrock layer (Vs = 2700 m/s) are smaller than those inferred from the logging model and the depth to the bedrock layer could be much deeper (about 600 m) in comparison with the logging model (234 m). The derived R/V spectral ratio at station KMMH16 also shows a distinct peak at 0.4 Hz, suggesting that there is no large difference of deep sedimentary structure between the observation area and station KMMH16.