Background: Nintendo® Wii-based therapy (NWT) is a non-immersive virtual reality therapy used to recover upper extremity (UE) motor function in children with cerebral palsy (CP). We aimed primarily to elucidate the effectiveness of NWT in improving UE motor and functional impaired abilities in children with CP, compared to conventional therapy or no intervention. The secondary aim was to assess if NWT is more effective when used alone or combined with conventional therapy. Methods: A systematic review with meta-analysis was conducted from a bibliographic search in PubMed, Scopus, PEDro, Web of Science, and CINHAL, ending in October 2021, in accordance with PRISMA guidelines. We included randomized controlled trials that compared NWT vs. conventional therapy or no intervention in terms of their impact on different UE impaired abilities (grip strength, tip grip strength, UE dissociated movements, functional capacity in daily living activities, gross and fine motor dexterity, and grasping ability) in children with CP. Effect size was calculated with standardized mean difference (SMD) and its 95% confidence interval (95% CI). Results: Nine studies (276 participants) were included. NWT is more effective than conventional therapy at improving grip strength (SMD = 0.5, 95% CI 0.08, 0.91), tip grip strength (SMD = 0.95, 95% CI 0.3, 1.61), and grasping ability (SMD = 0.72, 95%CI 0.14, 1.3). NWT is more effective than conventional therapy at improving functional capacity in daily living activities (SMD = 0.83, 95% CI 0.07, 1.56). For fine manual dexterity, NWT was better than no intervention (SMD = 3.12, 95% CI 1.5, 4.7). Conclusions: Our results indicate that NWT is effective at improving various UE impaired motor skills in children with CP.