Background As part of the multi-country I-O Optimise research initiative, this population-based study evaluated real-world treatment patterns and overall survival (OS) in patients treated for advanced non-small cell lung cancer (NSCLC) before and after public reimbursement of immuno-oncology (I-O) therapies in Alberta province, Canada. Methods This study used data from the Oncology Outcomes (O2) database, which holds information for ~ 4.5 million residents of Alberta. Eligible patients were adults newly diagnosed with NSCLC between January 2010 and December 2017 and receiving first-line therapy for advanced NSCLC (stage IIIB or IV) either in January 2010-March 2016 (pre–I-O period) or April 2016-June 2019 (post–I-O period). Time periods were based on the first public reimbursement of I-O therapy in Alberta (April 2017), with a built-in 1-year lag time before this date to allow progression to second-line therapy, for which the I-O therapy was indicated. Kaplan–Meier methods were used to estimate OS. Results Of 2244 analyzed patients, 1501 (66.9%) and 743 (33.1%) received first-line treatment in the pre–I-O and post–I-O periods, respectively. Between the pre–I-O and post–I-O periods, proportions of patients receiving chemotherapy decreased, with parallel increases in proportions receiving I-O therapies in both the first-line (from < 0.5% to 17%) and second-line (from 8% to 47%) settings. Increased use of I-O therapies in the post–I-O period was observed in subgroups with non-squamous (first line, 15%; second line, 39%) and squamous (first line, 25%; second line, 65%) histology. First-line use of tyrosine kinase inhibitors also increased among patients with non-squamous histology (from 26% to 30%). In parallel with these evolving treatment patterns, median OS increased from 10.2 to 12.1 months for all patients (P < 0.001), from 11.8 to 13.7 months for patients with non-squamous histology (P = 0.022) and from 7.8 to 9.4 months for patients with squamous histology (P = 0.215). Conclusions Following public reimbursement, there was a rapid and profound adoption of I-O therapies for advanced NSCLC in Alberta, Canada. In addition, OS outcomes were significantly improved for patients treated in the post–I-O versus pre–I-O periods. These data lend support to the emerging body of evidence for the potential real-world benefits of I-O therapies for treatment of patients with advanced NSCLC.