Carpal tunnel syndrome (CTS) refers to the symptoms and signs caused by the compression of the median nerve in the carpal tunnel. It can be treated by corticosteroid injection into the carpal tunnel. Two methods for injection have been employed, namely ultrasound-guided and landmark-guided injection. This systematic review and meta-analysis was conducted to compare these methods in terms of several outcomes. A search of the PubMed, Cochrane Library, and Embase databases was performed from the date of their inception to October 7, 2020 to identify randomized controlled trials (RCTs). Results for continuous variables are expressed as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Analyses were performed using RevMan 5.3 software. The analysis included eight RCTs published between 2013 and 2019 with a total of 448 patients. Ultrasound-guided injection yielded more favorable results than landmark-guided injection for the Boston Carpal Tunnel Syndrome Questionnaire, Symptom Severity Scale [SMD = - 0.43, 95% CI (- 0.68, - 0.19), P = 0.0005] and Boston Carpal Tunnel Syndrome Questionnaire, Functional Status Scale [SMD = - 0.50, 95% CI (- 0.84, - 0.15), P = 0.005]. Ultrasound-guided corticosteroid injection is recommended for patients with CTS.