The current COVID-19 pandemic is a novel, unprecedented situation that has created considerable uncertainty due in part to the unpredictability of the future situation. Intolerance of Uncertainty is the inability to withstand negative uncertain situations, and predisposes people to overestimate threats and to develop psychopathological symptoms. The aim of this study was to longitudinally analyze the relationship between intolerance of COVID-19-related uncertainty and anxiety and depression symptoms. A non-probabilistic online snowball sampling method was used. For the study, 1230 Argentine adults (216 men; 1005 women; 9 other genders; mean age = 41.62; SD = 13.81) were recruited to complete three open-access surveys at three different time points: (1) between May 6 and June 1, 2020, (2) between August 8 and 13, 2020, and (3) between April 17 and 23, 2021. The results suggest that anxiety and depressive symptoms increase over time, and that intolerance of uncertainty is a predictor of this variability even up to eleven months after the initial assessment. Gender- and age- related effects were also observed (women and young people reported more psychopathological symptoms). The findings suggest the importance of intolerance of uncertainty for mental health and the importance of this type of study for understanding the psychological impact of the pandemic.