Background: While cancer cachexia is associated with increased morbidity/mortality, little is known about longitudinal weight changes and opportunities for intervention pre- and post-diagnosis in this patient population. We therefore aimed to characterize body weight trajectories pre- and post- non-small cell lung cancer (NSCLC) diagnosis in patients without and with cachexia. Methods: Data were retrospectively extracted for each patient pre- and post-diagnosis of NSCLC from inpatient and outpatient visits within the UT Southwestern Medical Center Healthcare System. 3830 participants were screened with a NSCLC diagnosis between May 2005 to December 2019. Of these, 661 patients had a body weight recorded at cancer diagnosis and at least one body weight pre-diagnosis. The primary outcome was weight change over time. Other measures included defining associations between weight change and tumor pathology, stage of disease, and other clinical characteristics. Results: NSCLC patients without cachexia at cancer diagnosis were weight stable up to 12-months pre-diagnosis (+1.0±0.3% body weight; p = 0.01). Weight loss post-diagnosis was driven by stage of disease (stage 1/2: 0.4±0.5% body weight vs. stage 3/4: 4.8±0.9% body weight p = 0.0008) and treatment with chemotherapy (p < 0.0001). NSCLC patients with cachexia at cancer diagnosis lost weight pre-diagnosis (8.8±0.5% body weight; p < 0.0001), with 25% of this weight loss occurring between 6- and 12-months pre-diagnosis. Assessing weight change over 12 months opposed to 6 months resulted in a 32% increase in NSCLC patients with cachexia at cancer diagnosis (p = 0.006). By 12-months post-diagnosis, 62% of surviving late-stage and 45% of early-stage NSCLC patients had met the criteria for cachexia. Patients on average remained free of weight loss for 150±6.4 days or had pre-cachexia for 146±7.2 days prior to transitioning to a more advanced stage of the syndrome. Conclusions: Significant weight loss in NSCLC patients initiated as far back as 12 months prior to a cancer diagnosis as opposed to a shorter 6-month interval currently used to define patients with cachexia. Therefore, detection of earlier weight loss should be prioritized in high-risk NSCLC screening candidates. Finally, advanced NSCLC patients develop cachexia post-diagnosis irrespective of previous weight history, highlighting the impact of treatment iatrogenicity and/or refractory disease on cachexia development.