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Significant multi‐centennial climate oscillations have been documented in a number of well‐dated climate records across the Holocene epoch and left various imprints in human cultural history. In this study, we developed speleothem δ13C, δ18O, trace elements, and lamina thickness records from the Yunnan‐Guizhou Plateau (YGP). Our high‐resolution and precisely dated records show a significant ∼550‐yr cycle as the dominant pattern of regional temperature and vegetation variations between ∼5,870 and ∼3,670 years ago. The phase analyses of the 550‐yr cycles among our speleothem records, other Northern Hemisphere climate records, solar activity index, and Atlantic meridional overturning circulation (AMOC) variations suggest that this climate cycle has a large spatial extent, and may be causally linked to the AMOC changes through coupled oceanic‐atmospheric processes. Additionally, the first cold phase of the ∼550‐yr cycle in our records coincides with the major cultural development on the YGP at ∼5,500–5,000 years ago, suggesting a critical relationship between climate and prehistorical cultural changes in the region. Plain Language Summary: This study presents precisely dated speleothem isotope and lamina thickness records, which shows a ∼550‐yr periodicity of vegetation and temperature changes between ∼5,870 and ∼3,670 years ago in the Yunnan‐Guizhou Plateau (YGP), southwestern China. The phase analyses between our records and other Northern Hemisphere climate records suggest that these climate cycles have a large spatial scale in Northern Hemisphere and may be linked to the Atlantic meridional overturning circulation changes through coupled oceanic‐atmospheric processes. Besides, the records show that a cold phase during ∼5,500–5,000 years ago coincided with the period of development of YGP Neolithic production tools, suggesting a critical role of climate change in the prehistorical cultural evolution in the region. Key Points: A significant multi‐centennial temperature and vegetation oscillation of ∼550‐yr cycles occurred between ∼5,870 and ∼3,670 years ago in the Yunnan‐Guizhou Plateau (YGP)The climate cycles were likely linked to the Atlantic meridional overturning circulation variation through coupled oceanic‐atmospheric processesThe first cold phase of the ∼550‐yr cycles in our records coincided with a change of population and major cultural transform in the YGP at ∼5,500–5,000 years ago, implying a critical role of climate change and resource shortage in the prehistorical cultural evolution in the region [ABSTRACT FROM AUTHOR]