Background Fatigue remains a prevalent and debilitating symptom in persons with non-small cell lung cancer (NSCLC). Exercise has been shown to be effective in reducing fatigue; yet interventions are limited for post-surgical NSCLC patients. To date, while surgery is offered as a standard curative treatment for NSCLC, no formal guidelines exist for post-surgical rehabilitation. Objective This study focuses on the design and testing of a post-surgical intervention for NSCLC patients to promote perceived self-efficacy for fatigue self-management targeting cancer-related fatigue (CRF) severity and its associated fatigability through exercise. Interventions/ Methods A two-arm randomized controlled trial (RCT) was used to examine the impact of a 6-week rehabilitative CRF self-management exercise intervention on 37 NSCLC participants compared with 35 control group participants receiving usual care from diagnosis to 6 weeks post-surgical hospital discharge. Results We exceeded goals for recruitment (66%), retention (97%), adherence (93%), and acceptability. Our 6-week exercise intervention demonstrated preliminary efficacy in significantly reducing CRF severity and fatigability as compared to usual care, with mean CRF levels restored to levels lower than pre-surgery. Likewise, the exercise group's functional performance (physical and mental health scores) exceeded usual care. Further, no adverse events were reported; participants had a mean age of 67 and a mean of 8 comorbid conditions. Conclusions An exercise intervention for post-surgical NSCLC patients is feasible, safe, and highly acceptable showing positive changes in CRF self-management. Implications for Practice To advance practice, testing of the effectiveness of this health-promoting self-management exercise intervention in a larger-scale RCT.