The Atlantic and Gulf Coastal Plain in the southern and southeastern United States contains extensive Cretaceous and Cenozoic sedimentary sequences of variable thickness. We investigated the difference in response of sites in the Coastal Plain relative to sites outside that region using Fourier spectral ratios from 17 regional earthquakes occurring in 2010–2018 recorded by the Earthscope transportable array and other stations. We used mean coda and Lg spectra for sites outside the Coastal Plain as a reference. We found that Coastal Plain sites experience amplification of low‐frequency ground motions and attenuation at high‐frequencies relative to average site conditions outside the Coastal Plain. The spectral ratios at high frequencies gave estimates of the difference between kappa at Coastal Plain sites and the reference condition. Differential kappa values determined from the coda are correlated with the thickness of the sediment section and agree with previous estimates determined from Lg waves. Averaged estimates of kappa reach at Gulf coast stations overlying of sediments. Relations between Lg spectral ratio amplitudes versus sediment thickness in successive frequency bins exhibit consistent patterns, which were modeled using piecewise linear functions at frequencies ranging from 0.1 to 2.8 Hz. For sediment thickness greater than , the spectral amplitude ratio at frequencies higher than approximately is controlled by the value of kappa. The peak frequency and maximum relative amplification at frequencies less than depend on sediment thickness. At 0.1 Hz, the mean Fourier amplitude ratio (Coastal Plain/reference) is about 2.7 for sediment of 12 km thickness. Analysis of residuals between observed and predicted ground motions suggests that incorporating the amplification and attenuation as functions of sediment thickness may improve ground‐motion prediction models for the Coastal Plain region.