Underfloor air distribution (UFAD) systems are increasingly used for their advantages in improving energy savings, indoor air quality, and thermal comfort. In UFAD systems, an underfloor plenum delivers conditioned air to the air supply diffusers. The distribution of internal air velocity and static pressure in plenums determines the uniformity of the airflow to the occupied zones. As a result, the plenum has a detrimental effect on the characteristics of the supply air and, thus, the resulting indoor air quality and thermal comfort. Nevertheless, most existing studies on underfloor plenums focused on small-scale plenums with a single internal air duct. Large plenums and multiple air ducts in UFAD equipped in large premises are underexplored. In this study, a circular underfloor plenum with a large scale (radius of 15 m, height difference of 0.9−2.9 m) and 503 under-seat diffusers in a conference room was studied using computational fluid dynamics (CFD) simulation (ANSYS Fluent (16.0)). The distributions of airflow velocity and static pressure inside the plenum were analyzed and compared to one concentrated air supply mode and three uniform air supply modes. Based on the air velocity at the center of under-seat diffusers, the outgoing airflow uniformity from the diffusers under four cases was evaluated by the index of air velocity uniformity. The results showed that the multiple supply ducts with bottom air outlets yielded the best uniformity of supply air. The findings of this paper are expected to provide a technical basis for realizing the optimal design of the UFAD system in terms of uniformity of supply air.