Background: Only a few studies have reported on the risk factors for non-union after open reduction and internal fixation (ORIF) in distal humerus fractures. Methods: We retrospectively reviewed 155 patients who underwent ORIF for distal humerus fractures from January 2008 to June 2020. Various patient factors, including body mass index (BMI), diabetes mellitus (DM), and combined fracture, as well as surgical factors, including fixation methods (e.g., orthogonal plate/parallel plate/single plate/tension bend wiring [TBW]) and combined fracture operations, were evaluated as risk factors for non-unions. Results: Among the patient factors, BMI (25.0 ± 3.4 vs. 22.7 ± 3.4, p = 0.032), DM (5/13 [38.5%] vs. 20/142 [14.1%], p = 0.038) and combined fracture (5/13 [38.5%] vs. 16/142 [11.3%], p = 0.018) were significantly different between groups with non-union and union. Among the surgical factors, combined fracture operation (5 [38.5%] vs. 9 [6.3%], p = 0.002) and the fixation method (3 [23.1%]/1 [7.7%]/4 [30.8%]/5 [38.5%] vs. 84 [59.2%]/7 [4.9%]/40 [28.2%]/11 [7.7%], p = 0.005) showed a significant difference between groups with non-union and union. Multivariate regression analysis showed that combined fracture operation (OR 10.467; 95% CI 1.880–58.257; p = 0.007) and TBW (OR 9.176; 95% CI 1.474–57.135; p = 0.018) among the fixation methods posed as a significant risk factor for non-union. Conclusions: The risk of non-union increased in patients who underwent surgery for another fracture combined with distal humerus fracture and in patients who underwent ORIF with TBW.