Background The mechanism underlying tumor spread through air spaces (STAS) has not been well studied. We investigated the role of tumor stromal cells in the pathogenesis of STAS from a pathological perspective and evaluated the prognostic significance of tumor stromal cells and STAS in postoperative patients with lung adenocarcinoma. Methods We retrospectively analyzed 208 postsurgical patients with stage I-IIIA lung adenocarcinoma. The presence of STAS was evaluated by hematoxylin and eosin staining. The expression of alpha-smooth muscle actin (SMA)-positive cancer-associated fibroblasts (CAFs) and CD204-positive tumor-associated macrophages (TAMs) was analyzed by immunohistochemistry. A logistic regression model was applied to confirm the predictive factors of STAS. Survival analysis was performed to evaluate the effect of alpha-SMA-positive CAFs, CD204-positive TAMs, and STAS on prognosis. A nomogram was generated to evaluate the prognosis of postoperative patients. Results Logistic regression suggested that the expression of alpha-SMA-positive CAFs (P < 0.001) and the number of CD204-positive TAMs (P < 0.001) were related to the presence of STAS. The multivariate Cox proportional hazards model suggested that STAS (P = 0.004), alpha-SMA-positive CAFs (P < 0.001), and CD204-positive TAMs (P < 0.001) were independent risk factors for prognosis. Harrell's c-indexes for overall and recurrence-free survival prediction based on nomograms were 0.84 (95% confidence interval 0.76-0.91) and 0.82 (95% confidence interval 0.76-0.89), respectively. Conclusions The presence of STAS was associated with high expression of alpha-SMA and CD204 in lung adenocarcinoma. Nomograms including STAS and stromal cells as variables are recommended as practical models to evaluate the prognosis of lung adenocarcinoma patients.