Abstract Objectives This study aimed to estimate the incidence of adverse pregnancy outcomes (APO) in patients with systemic lupus erythematosus (SLE) and to evaluate the risks associated with immunosuppressant use—including hydroxychloroquine and teratogenic agents such as mycophenolate mofetil, methotrexate and cyclophosphamide—across specific APO categories. Methods A cohort study was conducted using the 2005–2018 National Health Information Database of the National Health Insurance Service in Korea, involving 4,880 pregnancies in 3,059 women with SLE. The incidences of preeclampsia/eclampsia, preterm birth, spontaneous abortion and stillbirth were estimated. Associations between APOs and medication patterns from preconception through pregnancy were analysed using univariate and multivariable models. Results The overall APO incidence among pregnant women with SLE was 45.0% (95% CI: 43.4, 46.5%). Compared with continuous hydroxychloroquine use, non-use (adjusted odds ratio [AOR]: 1.39; 95% CI: 1.05, 1.85), discontinuation (AOR: 2.18; 95% CI: 1.61, 2.95), and initiation during pregnancy (AOR: 2.17; 95% CI: 1.16, 4.06) were significantly associated with increased preterm birth risk. Exposure to teratogenic immunosuppressants within 3 months of preconception or during the first trimester was associated with increased spontaneous abortion risk (AOR: 2.59 and 3.18, respectively). Conclusion Continuity of hydroxychloroquine use from preconception through pregnancy reduces preterm birth risk in SLE. Conversely, early exposure to teratogenic immunosuppressants heightens the risk of spontaneous abortion. These findings underscore the importance of preconception medication planning in women with SLE.