Individuals with neurodevelopmental conditions (NDCs) have been reported to experience increased levels of anxiety during the COVID-19 pandemic. In our study, we document how individuals with Down Syndrome (DS; N = 557; Mage = 16.52; 233 female) and Williams syndrome (WS, N = 247; Mage = 18.43; 113 female) experienced the first wave (April 2020–May 2020) of the COVID-19 pandemic across the world. Using multilevel linear mixed regressions, we studied (a) parental reported anxiety of individuals with DS and WS, (b) these individuals’ specific concerns, and (c) their use and efficacy of emotion regulation (ER) strategies during the first wave of COVID-19. Predictors of anxiety, such as the age of the individual with NDC, type of condition, and time, were investigated. Individuals with WS experienced higher levels of anxiety compared to those with DS and the older the individuals with NDC were the more anxiety they experienced. In terms of concerns, group effects indicated that individuals with WS scored higher for most of the concerns. There were no gender differences in concerns, yet most of the concerns increased with age except for concerns about loss of routine, boredom, loss of institutional support and family conflict. Finally, significant group effects were found and indicated a more frequent use of a variety of adaptive and maladaptive ER strategies in individuals with WS. We did not identify group differences in the efficacy of ER strategies. Our results indicate that individuals with WS are likely to exhibit higher levels of anxiety, but also higher levels of concerns depending on their age. Similarly, individuals with WS use a variety of ER strategies more frequently but these strategies are not necessarily more efficient for them. We discuss the impact of these findings in relation to anxiety identification and support across individuals with NDCs.