Purpose <p>A randomized-controlled trial to investigate the efficacy of a 6-month self-paced aquatic exercise intervention on physical function, symptoms and psychosocial measures in individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).</p> Methods <p>Thirty-two individuals diagnosed with ME/CFS (55.0 ± 13.9&#xa0;yr) were randomized into an intervention group (INT, <i>n</i> = 17) or control group (CON, <i>n</i> = 15) for a 6-month trial of two 20-min sessions per week of self-paced aquatic movements and stretches. Pre- and post-intervention outcomes included physiological measures, 6-min walk test, hand-grip strength, Sit-to-Stand, Apley’s shoulder test, Sit–Reach test, perceived exertion, fatigue (FACIT), anxiety/depression (HADS) questionnaires, and tiredness and pain scores (VAS 0–10 scale).</p> Results <p>The INT group significantly increased walk test distance (13.7%, <i>P</i> &lt; 0.001), Sit-to-Stand scores (33.7%, <i>P</i> &lt; 0.001) and peak expiratory pulmonary flow (12.9%, <i>P</i> = 0.028) post-intervention. Fatigue (29.5%, <i>P</i> = 0.005), depression (21.7%, <i>P</i> = 0.010), combined anxiety/depression scores (16.9%, <i>P</i> = 0.047) and resting diastolic blood pressure (4.8%, <i>P</i> &lt; 0.001) also significantly improved for the INT group. Sit–Reach scores were significantly lower for the INT group compared to CON post-intervention (− 4.0 ± 10.4 vs + 4.3 ± 10.7&#xa0;cm, <i>P</i> = 0.034). There were no adverse events or worsening of symptoms during the trial.</p> Conclusions <p>Self-paced, low–moderate-intensity aquatic exercise improved walk distance, lower limb strength, fatigue, depression and peak expiratory flow without worsening ME/CFS symptoms. This mode of low-intensity physical activity may confer mental health and physical benefits provided the activity is self-paced and within patient energy limits.</p> Trial registration number <p>Australian and New Zealand Clinical Trials Registry ANZCTRN12618001683224.</p>