Objectives This study aimed at evaluating the effect of genicular nerve block (GNB) in juvenile idiopathic arthritis (JIA) patients with persistent unilateral knee arthritis on pain, inflammatory parameters, function, and range of motion. Methods A total of 104 JIA patients were diagnosed according to the International League Against Rheumatism (ILAR) criteria with persistent unilateral knee arthritis. They were allocated randomly into 2 groups: group 1 treated with GNB, while group 2 was treated with intra-articular triamcinolone (TA) only. Visual analogue scale (VAS) on pain, sonography of large joints in rheumatology (SOLAR) scoring system, and Lysholm scores were assessed at 0-, 2-, and 12-week intervals. Swelling and tenderness were clinically evaluated semi-quantitatively (0-3) at the same time intervals. Results VAS pain, tenderness, swelling, and SOLAR grey scale (GS) and power Doppler (PD) scores were significantly reduced after 2 weeks in both groups (p < 0.05). This was greater in the GNB group regarding VAS and tenderness, while SOLAR and swelling were stronger reduced in TA group. After 12 weeks, all outcome measures showed lower values in the GNB group compared to TA, and this was significant regarding VAS pain. Moreover, Lysholm functional score was significantly increased in both groups at both intervals; and higher values were seen in the TA group compared to GNB after 2 weeks. Conclusion GNB was able to control pain and improve function and inflammation of the knee joint in JIA patients. Though steroid attained better results after 2 weeks, GNB achieved an equivalent longer-term improvement after 12 weeks. Trial registration identifying number NCT04687930. Key Points• Persistent knee arthritis treatment in JIA is always challenging.• GNB was approved for treatment of pain in knee osteoarthritis.• GNB in the present study succeeded to control active knee arthritis and this effect was comparable to intra-articular steroid injection.