The Ninetyeast Ridge (NER), one of the longest linear volcanic features on the Earth, offers an excellent opportunity of understanding the isostatic response to the interactions of mantle plume with the migrating mid-ocean ridge. Bathymetry, geoid, and gravity (shipborne and satellite) data along 72 closely spaced transects and 17 overlapping grids on the NER are analyzed and modeled to determine the effective elastic thickness (Te) beneath the entire ridge. The results of 2-D and 3-D flexural modeling of the NER show large spatial variations in Te values ranging from 4 to 35 km, suggesting that the ridge was compensated along its length by different isostatic mechanisms. The southern (south of 22°S latitude) and northern (north of 2°N latitude) parts of the NER have Te values of >10 and >23 km, respectively, revealing that the southern part was emplaced on a lithosphere of intermediate strength possibly on flank of the Indian plate, whereas the northern part was emplaced in an intraplate setting. In contrast, in the central part of the NER (between latitudes 22°S and 2°N), highly variable Te values (4–22 km) are estimated. The scattered Te values in the central NER suggest that this part may have evolved due to the occurrence of frequent ridge jumps caused by the interaction of Kerguelen hot spot with rapid northward migration of the Wharton spreading ridge. Residual Mantle Bouguer Anomaly (RMBA) map of the NER and adjacent basins reveals that the entire length of the NER is associated with a significant negative anomaly up to 200 mGal, indicating the presence of thickened crust or less dense mantle beneath the ridge. 3-D crustal thickness map of the NER, generated by inversion of the RMBA data, shows a thick crust ranging from 15 to 19 km. The present study clearly shows that NER possesses a highly segmented isostatic pattern with the occurrence of subcrustal underplating or subsurface loading.