Background eHealth interventions have been postulated as a feasible, acceptable, and possibly effective tool to promote physical activity (PA) among children and adolescents; however, a comprehensive quantitative analysis of the effects of eHealth interventions promoting PA is lacking. Objective This study aims to conduct a systematic review and meta-analysis on experimental studies reporting the effects of eHealth interventions aimed at promoting PA on PA parameters and sedentary behavior parameters in children and adolescents. Methods The CENTRAL, MEDLINE, Embase, and Web of Science databases were searched from inception to February 2022 for randomized controlled trials that analyzed the effects of eHealth interventions aimed at promoting PA on PA and sedentary parameters in children and adolescents. The Hartung-Knapp-Sidik-Jonkman random effects method was used to determine the mean differences (MDs) with their respective 95% CIs. The risk of bias was assessed using the Risk of Bias 2 (RoB2; Cochrane) tool and its extension for cluster randomized controlled trials. The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. Results A total of 20 trials reporting the effects of different eHealth interventions aimed at promoting PA were included. Results for each parameter were as follows: counts per minute (MD −16.11 counts, 95% CI −122.76 to 90.53; k=3; n=402; I2=69%; favoring control), steps per day (MD 593.46 steps, 95% CI −2102.27 to 3289.19; k=2; n=152; I2=0%; favoring intervention [FI]), moderate to vigorous PA (MD −1.99 min/d, 95% CI −8.95 to 4.96; k=14; n=2336; I2=86%; favoring control), light PA (MD 3.28 min/d, 95% CI −15.48 to 22.04; k=5; n=355; I2=67%; FI), screen time (MD −31.48 min/d, 95% CI −68.62 to 5.65; k=5; n=904; I2=0%; FI), and sedentary time (MD −33.12 min/d, 95% CI −57.27 to −8.97; k=8; n=819; I2=75%; FI). Our results should be interpreted cautiously because of important limitations such as the scarcity of evidence, overall risk of bias, and low to very low certainty of evidence. Conclusions We did not find conclusive evidence regarding the impact of PA-targeted eHealth interventions on PA parameters, but the very low certainty of evidence suggests that eHealth interventions may reduce sedentary time in children and adolescents. Our results may have important scientific implications as they highlight that the rapid development of eHealth interventions to promote PA lacks robust supporting evidence. Trial Registration PROSPERO CRD42020211020; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=211020