The S mutation of the β-globin gene (HBB*S) in humans is a well-studied example of an advantageous allele with a protective role against malaria in the heterozygous carrier state. More than 50 years ago, Livingstone proposed that the emergence of tropical agriculture provided ideal habitats for the spread of malaria-transmitting mosquitoes allowing the rapid diffusion of a single, relatively recent HBB*S mutation. However, the concept of a single mutation was challenged by the finding that different HBB*S-linked haplotypes predominated in various non-overlapping geographical regions of Africa, India and the Arabian Peninsula. Currently, the most favored hypothesis explaining the geographic segregation of HBB*S-linked haplotypes is that HBB*S variants originated independently by recurrent mutation in each region where a single haplotype predominates. However, little work has been done to explicitly examine the effects of the spatial diffusion of the HBB*S allele on linked haplotype variation. Here, we explored a computer simulation framework to assess the evolution of HBB*S-linked haplotype variation in time and space, using a stepping stone model for the dispersal of an advantageous allele under different demographic scenarios. Moreover, we compared the simulated scenarios with an empirical dataset, consisting of 330 high resolution HBB*S-linked haplotypes defined by 11 microsatellites distributed across a 525 kb region. We show that the wave of advance of the HBB*S allele can originate patterns that mimic the spatial distribution of S-haplotypes, by creating several patches (or sectors), each formed by contiguous populations that share unique S-linked modal haplotypes exhibiting levels of haplotype diversity that are compatible with those currently observed in Africa. These findings bring back the hypothesis of a single origin as a plausible explanation for the evolution of the S mutation.