Background: To fight against the rising incidence of syphilis, the Brazilian Ministry of Health (MoH) launched the "Syphilis No!" Project (SNP), with specific resources funded by a parliamentary amendment. Then, in 2018, a national rapid response started to be implemented on the Brazilian Unified Health System (SUS, Sistema Único de Saúde) in two strategic lines (1) to reinforce SUS's universal actions and (2) to implement specific ones to 100 municipalities chosen by the MoH as priorities for syphilis congenital response. In 2015, such localities represented 6895% of congenital syphilis cases in Brazil. In this context, SNP has implemented actions to strengthen epidemiological surveillance of acquired syphilis and congenital syphilis by instituting an integrated and collaborative response through health services networks and reinforcing interstate relations. Methods: A quasi-experimental study using time series analysis was conducted to assess immediate impacts and changes to the trend in national congenital syphilis before and after the project, from September 2016 to December 2019. Data were assessed considering rates of congenital syphilis per 1,000 live births in all priority municipalities (n=100) covered by the project and in non-priority municipalities (n=5,470) from all five macro-regions of Brazil. Findings: Priority municipalities showed a greater reduction (change in trend) in comparison to non-priority. The linear regression model revealed trend changes after the intervention, with both groups of municipalities showing a drop in the average monthly number of cases per 1,000 live births, with a reduction of -0·21 (CI 95% -0·33 to -0·09; p=0·0011) in priority municipalities and of -0·10 (CI 95% -0.19 to -0.02; p=0·0216) in non-priority municipalities. Interpretation: The study using ITS provides important evidence on the direction, timing, and magnitude of the effects of interventions introduced as part of the SNP on congenital syphilis in Brazil. Our results suggest that the Syphilis No! Project influenced the trends of congenital syphilis in Brazil from 2018, with higher reductions achieved in the priority municipalities. Funding: The research is funded by a grant to the Syphilis No! Project from Brazilian Ministry of Health (Project Number: 54/2017). The funders had no role in study design, analysis, decision to publish, or preparation of the manuscript.