Background: There is an ongoing debate about the role of perioperative chemotherapy in retroperitoneal sarcoma (RPS). The aim of this study was to evaluate the effectiveness of perioperative chemotherapy in subtypes of RPS that are considered chemosensitive, including retroperitoneal angiosarcoma, undifferentiated pleomorphic sarcoma, myxoid liposarcoma, spindle cell sarcoma, and synovial sarcoma. Methods: This is a population-based retrospective cohort study. Patients with localized retroperitoneal sarcoma who underwent surgery were included from the US National Cancer Database (NCDB). After propensity score matching for the factors age, sex, grade, margin status, and tumor size, multivariable logistic and Cox regression analyses were used to identify factors associated with systemic therapy and their potential impact on the survival of patients with localized RPS. Results: We included 851 patients who underwent surgery between 2004 and 2020 (85% white, 41% female, and mean age 62 years). Of those, 227 patients (26.7%) received perioperative chemotherapy. In multivariable logistic regression, age ≤ 60 and tumor grading GIII/IV vs. GI/II were associated with a higher probability of receiving perioperative chemotherapy. After propensity score matching, we detected no difference in overall survival between patients who received chemotherapy and those who did not (HR 0.89, CI 0.55–1.43; and log-rank p = 0.92). Patient age ≤80 and tumor grading GI/II vs. GIII/IV were associated with improved overall survival. Conclusions: In this large analysis, the use of perioperative chemotherapy was not associated with improved survival in rare, chemosensitive subtypes of retroperitoneal sarcoma. However, selection bias must be considered when interpreting these findings.