Smoking is the main preventable cause of illness and early death worldwide. Thus, it is better to promote smoking cessation than to treat tobacco-related diseases. The objective of this study was to assess the implementation and effectiveness of smoking cessation pharmaceutical services offered in primary health care (PHC) in a large Brazilian city through a type 1 effectiveness–implementation hybrid study. The services were offered through individual or group approaches (Jan/2018–Dec/2019). The service indicators were described and the incidence of cessation in the services was evaluated. Factors associated with cessation were assessed by Poisson regression analysis. The services were offered in most PHC centers (61.2%) and by most pharmacists (81.3%). In total, 170 individual (9.7%) and 1591 group (90.3%) approaches occurred, leading to cessation in 39.4% (n = 67) and 44.8% (n = 712) of these, respectively. The use of nicotine plus antidepressants (RR = 1.30; 95%CI = 1.08–1.57; p = 0.006) and the number of sessions with pharmacists (RR = 1.21; 95%CI = 1.19–1.23; p < 0.001) were positively associated with cessation; a very high level of dependence was negatively associated (RR = 0.77; 95%CI = 0.67–0.89; p = 0.001). The smoking cessation services were effective and should be encouraged.