This article presents one of the largest and broadest investigations into COVID-19 vaccine hesitancy, a burning issue that poses a global threat. First, I provide a timely review of the predictors of COVID-19 vaccine hesitancy identified by prior studies. More importantly, I advance a dynamic, cultural psychological perspective to examine how the cultural dimension of uncertainty avoidance partly explains national differences in initial vaccine hesitancy. To track global vaccine hesitancy over time, I leveraged a daily survey of 979,971 individuals in 67 countries/territories (October 2020 to March 2021) and another daily survey of over 11 million individuals in 244 countries/territories (December 2020 to March 2021). To increase sample representativeness, both surveys used algorithms to correct for nonresponse bias and coverage bias. Consistent with my theoretical perspective, people in higher (vs. lower) uncertainty avoidance cultures had higher vaccine hesitancy initially (late 2020) as a function of greater vaccine side-effect concerns, but these differences decreased over time as COVID-19 vaccine uptake became prevalent. These findings were robust after controlling for other cultural dimensions, demographics, COVID-19 severity, government response stringency, socioeconomic indicators, common vaccine coverage, and religiosity. Understanding cultural differences in vaccine hesitancy is important, as delaying vaccination for even a short period can increase morbidity and mortality. (PsycInfo Database Record (c) 2023 APA, all rights reserved).