Knowledge on the impact of neoadjuvant and adjuvant treatments on post-surgery lymphedema (LE) in patients with breast cancer is limited due to methodological limitations and an insufficient sample size. We investigated the risk of LE in patients going through long-term anticancer treatment regimens using a national cohort from the Korean National Health Insurance Service database from 2011–2013. Incidence rate ratio, Kaplan–Meier analysis, and Cox proportional regression analysis were performed. A total of 39,791 patients were included. While minimal lymph node dissection (SLNB) reduced the risk of LE (hazard ratio [HR] 0.51) as expected, neoadjuvant chemotherapy (NAC) followed by SLNB did not reduce the risk. Adjusting for adjuvant chemotherapy (AC) as time-varying exposure decreased the risk of LE in the SLNB group (HR 0.51), but not the mortality risk (HR 0.861). A longer duration of NAC, especially taxane-based, combined with SLNB reversed the effect and increased risk of LE. The findings highlight the importance of not only early surveillance before and after surgery, but also long-term surveillance during adjuvant treatment by surgeons and oncologists in order to reduce the risk of LE.