Previous studies have proposed that selection has been involved in the differentiation of human mitochondrial DNA (mtDNA) and climate was the main driving force. This viewpoint, however, gets no support from the subsequent studies and remains controversial thus far. To clarify this issue, a total of 237 complete mtDNA sequences belonging to autochthonous lineages from South Asia, Oceania, and East Asia were collected to seek for the imprint of selection. Based on nonsynonymous (N) and synonymous (S) substitutions analysis, our results confirmed that purifying selection was the predominant force during the evolution of human mtDNA. However, no significant and extensive difference was detected among these three regions, which did not support the climate adaptation hypothesis but preferred random genetic drift to be the main factor in shaping the current landscape of human mtDNA, at least those from Asian and Oceanian regions.