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Monsoon and arid regions in the Asia-Africa-Australia (A-A-A) realm occupy more than 60% of the total area of these continents. Geological evidence showed that significant changes occurred to the A-A-A environments of the monsoon and arid regions, the land-ocean configuration in the Eastern Hemisphere, and the topography of the Tibetan Plateau (TP) in the Cenozoic. Motivated by this background, numerical experiments for 5 typical geological periods during the Cenozoic were conducted using a coupled ocean-atmosphere general circulation model to systemically explore the formations and evolutionary histories of the Cenozoic A-A-A monsoon and arid regions under the influences of continental drift and plateau uplift. Results of the numerical experiments indicate that the timings and causes of the formations of monsoon and arid regions in the A-A-A realm were very different. The northern and southern African monsoons existed during the mid-Paleocene, while the South Asian monsoon appeared in the Eocene after the Indian Subcontinent moved into the tropical Northern Hemisphere. In contrast, the East Asian monsoon and northern Australian monsoon were established much later in the Miocene. The establishment of the tropical monsoons in northern and southern Africa, South Asia, and Australia were determined by both the continental drift and seasonal migration of the Inter-Tropical Convergence Zone (ITCZ), while the position and height of the TP were the key factor for the establishment of the East Asian monsoon. The presence of the subtropical arid regions in northern and southern Africa, Asia, and Australia depended on the positions of the continents and the control of the planetary scale subtropical high pressure zones, while the arid regions in the Arabian Peninsula and West Asia were closely related to the retreat of the Paratethys Sea. The formation of the mid-latitude arid region in the Asian interior, on the other hand, was the consequence of the uplift of the TP. These results from this study provide insight to the important roles played by the earth's tectonic boundary conditions in the formations and evolutions of regional climates during geological times.