Public health officials discouraged travel and non-household gatherings for Thanksgiving, but data suggests that travel increased over the holidays. The objective of this analysis was to assess associations between holiday gatherings and SARS-CoV-2 positivity in the weeks following Thanksgiving. Using an online survey, we sampled 7770 individuals across 10 US states from December 4–18, 2020, about 8–22 days post-Thanksgiving. Participants were asked about Thanksgiving, COVID-19 symptoms, and SARS-CoV-2 testing and positivity in the prior 2 weeks. Logistic regression was used to identify factors associated with SARS-CoV-2 positivity and COVID-19 symptoms in the weeks following Thanksgiving. An activity score measured the total number of non-essential activities an individual participated in the prior 2 weeks. The probability of community transmission was estimated using Markov Chain Monte Carlo (MCMC) methods. While 47.2% had Thanksgiving at home with household members, 26.9% had guests and 25.9% traveled. There was a statistically significant interaction between how people spent Thanksgiving, the frequency of activities, and SARS-CoV-2 test positivity in the prior 2 weeks (p < 0.05). Those who had guests for Thanksgiving or traveled were only more likely to test positive for SARS-CoV-2 if they also had high activity (e.g., participated in > one non-essential activity/day in the prior 2 weeks). Had individuals limited the number and frequency of activities post-Thanksgiving, cases in surveyed individuals would be reduced by > 50%. As travel continues to increase and the more contagious Delta variant starts to dominate transmission, it is critical to promote how to gather in a “low-risk” manner (e.g., minimize other non-essential activities) to mitigate the need for nationwide shelter-at-home orders.