Background Vaccination is an important intervention to prevent the incidence and spread of serious diseases. Many factors including information obtained from the internet influence individuals’ decisions to vaccinate. Misinformation is a critical issue and can be hard to detect, although it can change people's minds, opinions, and decisions. The impact of misinformation on public health and vaccination hesitancy is well documented, but little research has been conducted on the relationship between the size of the population reached by misinformation and the vaccination decisions made by that population. A number of fact-checking services are available on the web, including the Islander news analysis system, a free web service that provides individuals with real-time judgment on web news. In this study, we used such services to estimate the amount of fake news available and used Google Trends levels to model the spread of fake news. We quantified this relationship using official public data on COVID-19 vaccination in Taiwan. Objective In this study, we aimed to quantify the impact of the magnitude of the propagation of fake news on vaccination decisions. Methods We collected public data about COVID-19 infections and vaccination from Taiwan's official website and estimated the popularity of searches using Google Trends. We indirectly collected news from 26 digital media sources, using the news database of the Islander system. This system crawls the internet in real time, analyzes the news, and stores it. The incitement and suspicion scores of the Islander system were used to objectively judge news, and a fake news percentage variable was produced. We used multivariable linear regression, chi-square tests, and the Johnson-Neyman procedure to analyze this relationship, using weekly data. Results A total of 791,183 news items were obtained over 43 weeks in 2021. There was a significant increase in the proportion of fake news in 11 of the 26 media sources during the public vaccination stage. The regression model revealed a positive adjusted coefficient (β=0.98, P =.002) of vaccine availability on the following week's vaccination doses, and a negative adjusted coefficient (β=–3.21, P =.04) of the interaction term on the fake news percentage with the Google Trends level. The Johnson-Neiman plot of the adjusted effect for the interaction term showed that the Google Trends level had a significant negative adjustment effect on vaccination doses for the following week when the proportion of fake news exceeded 39.3%. Conclusions There was a significant relationship between the amount of fake news to which the population was exposed and the number of vaccination doses administered. Reducing the amount of fake news and increasing public immunity to misinformation will be critical to maintain public health in the internet age.