The purpose of this systematic review and meta-analysis was to examine the effects of exercise training on muscle sympathetic nerve activity (MSNA) in humans. Studies included exercise interventions [randomized controlled trials (RCTs), nonrandomized controlled trials (non-RCTs), or pre-to-post intervention] that reported on adults (≥18 yr) where MSNA was directly assessed using microneurography, and relevant outcomes were assessed [MSNA (total activity, burst frequency, burst incidence, amplitude), heart rate, blood pressure (systolic blood pressure, diastolic blood pressure, or mean blood pressure), and aerobic capacity (maximal or peak oxygen consumption)]. Forty intervention studies (n = 1,253 individuals) were included. RCTs of exercise compared with no exercise illustrated that those randomized to the exercise intervention had a significant reduction in MSNA burst frequency and incidence compared with controls. This reduction in burst frequency was not different between individuals with cardiovascular disease compared with those without. However, the reduction in burst incidence was greater in those with cardiovascular disease [9 RCTs studies, n = 234, mean difference (MD) -21.08 bursts/100 hbs; 95% confidence interval (CI) -16.51, -25.66; I2 = 63%] compared with those without (6 RCTs, n = 192, MD -10.92 bursts/100 hbs; 95% CI -4.12, -17.73; I2 = 76%). Meta-regression analyses demonstrated a dose-response relationship where individuals with higher burst frequency and incidence preintervention had a greater reduction in values post-intervention. These findings suggest that exercise training reduces muscle sympathetic nerve activity, which may be valuable for improving cardiovascular health.NEW & NOTEWORTHY This systematic review and meta-analysis suggests exercise training reduces muscle sympathetic nerve activity (MSNA), which may be valuable for improving cardiovascular health. The reduction in burst incidence was greater among individuals with cardiovascular disease when compared with those without; exercise training may be particularly beneficial for individuals with cardiovascular disease. Meta-regression analyses demonstrated a dose-response relationship, where individuals with higher sympathetic activity preintervention had greater reductions in sympathetic activity post-intervention.