Increasing numbers of individuals suffer from post-acute COVID-19 syndrome (PACS), which manifests with persistent symptoms, the most prevalent being dyspnea, fatigue, and musculoskeletal, cognitive, and/or mental health impairments. This systematic review investigated the effectiveness of rehabilitation interventions for individuals with PACS. We searched the MEDLINE, Embase, Cochrane Register of Controlled Trials, CINHAL, Scopus, Prospero, and PEDro databases and the International Clinical Trials Registry Platform for randomized controlled trials (RCTs) up to November 2021. We screened 516 citations for eligibility, i.e., trials that included individuals with PACS exposed to exercise-based rehabilitation interventions. Five RCTs were included, accounting for 512 participants (aged 49.2–69.4 years, 65% males). Based on the revised Cochrane risk-of-bias tool (RoB 2.0), two RCTs had “low risk of bias”, and three were in the “some concerns” category. Three RCTs compared experimental rehabilitation interventions with no or minimal rehabilitation, while two compared two active rehabilitation interventions. Rehabilitation seemed to improve dyspnea, anxiety, and kinesiophobia. Results on pulmonary function were inconsistent, while improvements were detected in muscle strength, walking capacity, sit-to-stand performance, and quality of life. Pending further studies based on qualitatively sound designs, these first findings seem to advocate for rehabilitation interventions to lessen disability due to PACS.