Intra-articular corticosteroid and hyaluronic acid injections provide short-term symptom amelioration for arthritic conditions involving structural damage or degenerative changes in the knee. Conventional palpation-guided anatomical injections frequently result in inaccurate needle placement into extra-articular tissue and adjacent structures. The purpose of this review was to determine the effect of ultrasound guidance on the accuracy of needle placement, clinical outcomes, and cost-effectiveness in comparison with anatomical landmark-guided intra-articular large joint injections, with particular emphasis on the knee. A total of 13 relevant studies were identified; five studied the knee, seven studied the shoulder, one used both the knee and shoulder, and none studied the hip. Ultrasound was used in seven studies; the remaining studies utilized air arthrography, fluoroscopy, magnetic resonance arthrography, or magnetic resonance imaging. Across all studies (using all imaging modalities and all joints), needle placement accuracy ranged from 63% to 100% with ultrasound and from 39% to 100% with conventional anatomical guidance. Imaging guidance improved the accuracy of intra-articular injections of the knee (96.7% versus 81.0%, P < 0.001) and shoulder (97.3% versus 65.4%, P < 0.001). In particular, ultrasound guidance of knee injections resulted in better accuracy than anatomical guidance (95.8% versus 77.8%, P < 0.001), yielding an odds ratio of 6.4 (95% confidence interval 2.9–14). Ultrasound guidance notably improves injection accuracy in the target intra-articular joint space of large joints including the knee. The enhanced injection accuracy achieved with ultrasound needle guidance directly improves patient-reported clinical outcomes and cost-effectiveness.