Purpose <p>To investigate the longitudinal changes in lung function of sedentary middle-aged workers over a 16-week combined exercise training program.</p> Methods <p>Thirty-six sedentary workers (53.70 ± 6.92&#xa0;years old) were randomly allocated to either a combined aerobic and resistance training program (n = 18) or a control group (n = 18). Lung function was evaluated through spirometry using a portable flow spirometer (Spiropalm 6MWT, Cosmed, Italy). Predicted percentages of forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁), FEV₁/FVC ratio, and mean forced expiratory flow between 25 and 75% of exhaled FVC (FEF_25–75) were analyzed. Assessments were performed at baseline (M1), after 8-week (M2) and 16-week follow-up (M3). The changes in lung function were analyzed using the Latent Growth Curve Modeling that estimated interindividual and intraindividual growth paths.</p> Results <p>Smoking status revealed a significant effect on lung function growth with significant paths to intercept and slope for all models in both groups. The exercise group participants who are non-smokers revealed higher increases in FVC% (<i>β</i> = .22), FEV₁% (<i>β</i> = .08), FEV₁/FVC% ratio (<i>β</i> = .19), and FEF_25–75% (<i>β</i> = .06) compared to those who are smokers from M1 to M3. The control group revealed a lower growth in lung function from M1 to M3, with a lower slope observed in smokers compared to non-smokers for FVC% (<i>β</i> = − .44), FEV₁% (<i>β</i> = −.41), FEV₁/FVC% (<i>β</i> = − .98), and FEF_25–75% (<i>β</i> = − .52).</p> Conclusion <p>Our findings suggest that a 16-week combined training program is an effective strategy to improve lung function among sedentary workers, with a higher magnitude of improvement for non-smokers compared to smokers.</p> <b>Trial registration</b> <p>Clinicaltrials.gov, NCT04868240. Registered April 30, 2021.</p>