The beginning of the COVID-19 pandemic was marked by a sharp decline in syphilis infections in many countries worldwide, including Greece. However, a resurgence of positive cases started to appear in the second half of 2020. The aim of this study was to explore the impact of the pandemic on the incidence of new syphilis infections and reinfections and analyze the sociodemographic characteristics associated with recurrent episodes. We analyzed medical records from a 14-month period after the beginning of the pandemic and compared them with the respective period before the start of the pandemic. Our participants consisted mainly of men, with a median age of 43 years, homosexual orientation, and higher education. During COVID-19, more HIV patients presented for syphilis testing (38.0% vs. 34.6%, p = 0.025). Overall, we observed almost a two-fold increase in positive syphilis cases during COVID-19 (21.1% vs. 12.4%, p < 0.001), with new infections rising from 8.4% to 13.2% and reinfections from 4.0% to 7.9%. Multivariable logistic regression analysis revealed that the COVID-19 pandemic, among different parameters (such as age, gender, sexual orientation, HIV status, and educational level), was the only factor associated with higher positive syphilis rates (OR 1.47, 95% CI: 1.07–2.01, p = 0.003). Our results highlight the need to ensure enhanced prevention and undisrupted healthcare services, with a focus on future pandemics.