Abstract Objective Lung adenocarcinoma exhibits diverse genetic and morphological backgrounds, in addition to considerable differences in clinical pathology and molecular biological characteristics. Among these, the phenomenon of spread through air space (STAS), a distinct mode of lung cancer infiltration, has rarely been reported. Therefore, this study aimed to explore the relationship between STAS tumor cells and the clinical and molecular characteristics of patients with lung adenocarcinoma, as well as their impact on prognosis. Methods This study included 147 patients who were diagnosed with lung adenocarcinoma at the Inner Mongolia Autonomous Region Cancer Institute between January 2014 and December 2017. Surgical resection specimens were retrospectively analyzed. Using univariate and multivariate Cox analyses, we assessed the association between STAS and the clinicopathological features and molecular characteristics of patients with lung adenocarcinoma. Furthermore, we investigated the effects on patient prognosis. In addition, we developed a column–line plot prediction model and performed internal validation. Results Patients with positive STAS had a significantly higher proportion of tumors with a diameter ≥2 cm, with infiltration around the pleura, blood vessels, and nerves, and a pathological stage >IIB than in STAS-negative patients (P < 0.05). Cox multivariate survival analysis revealed that clinical stage, STAS status, tumor size, and visceral pleural invasion were independent prognostic factors influencing the 5-year progression-free survival in patients with lung adenocarcinoma. The predictive values and P values from the Hosmer-Lemeshow test were 0.8 and 0.2, respectively, indicating no statistical difference. Receiver operating characteristic curve analysis demonstrated areas under the curve of 0.884 and 0.872 for the training and validation groups, respectively. The nomogram model exhibited the best fit with a value of 192.09. Conclusions Clinical stage, pleural invasion, vascular invasion, peripheral nerve invasion, tumor size, and necrosis are independent prognostic factors for patients with STAS-positive lung adenocarcinoma. The nomogram based on the clinical stage, pleural invasion, vascular invasion, peripheral nerve invasion, tumor size, and necrosis showed good accuracy, differentiation, and clinical practicality.