The Swietenia macrophylla King (Meliaceae) mahogany tree is widely spread in the neotropics. In Ecuador, it has a wide distribution range from the coastal zone to the Amazon. The mahogany tree is an endangered species due the overexploitation of the high commercial value of its wood. This study is aimed to characterize the Simple Sequence Repeat (SSR) variability of 123 trees selected from six provinces of Ecuador. The results showed that the natural mahogany population had a low level of genetic diversity (A = 6.9; Ho = 0.39; He = 0.43) and a significant heterozygous deficit inbreeding coefficient (F = 0.16). The probability of identity (PI) of the 12 microsatellite markers was low 4.3 × 10−9 and the cumulative exclusion probability of 99.99%. Additionally, the relatedness coefficient among individuals was −0.010 (se = 0.004). The genetic diversity among populations was moderate (ΦST = 8%). In addition, the structure analysis showed two genetic groups; however, it was possible to distinguish admixture within the entire range evaluated. These results show the need to establish strategies that allow the recovery and increase of the genetic diversity in natural populations, especially with the selection of trees to harvest seeds, as well as crossing the tree genetic pool to recombine their diversity.