Effective treatments for smoking cessation exist but are underused. Proactive chronic care approaches may enhance the reach of cessation treatment and reduce the prevalence of smoking in healthcare systems. This pragmatic study evaluated a population-based Comprehensive Tobacco Intervention Program (CTIP) implemented in all (6) adult primary care clinics in a Madison, Wisconsin, USA healthcare cooperative, assessing treatment reach, reach equity, and effectiveness in promoting smoking cessation. CTIP launched in 3 waves of 2 clinics each in a multiple baseline design. Electronic health record (EHR) tools facilitated clinician-delivered pharmacotherapy and counseling; guiding tobacco care managers in phone outreach to all patients who smoke; and prompting multimethod bulk outreach to all patients on a smoking registry using an opt-out approach. EHR data were analyzed to assess CTIP reach and effectiveness among 6894 adult patients between January 2018 and February 2020. Cessation treatment reach increased significantly after CTIP launch in 5 of 6 clinics and was significantly higher when clinics were active vs. inactive in CTIP [Odds Ratio (OR) range = 2.0-3.0]. Rates of converting from current to former smoking status were also higher in active vs. inactive clinics (OR range = 2.2-10.5). Telephone treatment reach was particularly high in historically underserved groups, including African-American, Hispanic, and Medicaid-eligible patients. Implementation of a comprehensive, opt-out, chronic-care program aimed at all patients who smoke was associated with increases in the rates of pharmacotherapy and counseling delivery and quitting smoking. Proactive outreach may help reduce disparities in treatment access.