In this paper, a three-dimensional numerical investigation was performed for heat transfer characteristics and flow structure of full scale fin-and-tube heat exchangers with rectangular winglet pair (RWP). For the Reynolds number ranging from 500 to 880, the baseline configuration (without RWP) is compared with three enhanced configurations (with RWP): inline-1RWP case, inline-3RWP case, and inline-7RWP case. It was found that the air-side heat transfer coefficient improved by 28.1–43.9%, 71.3–87.6%, and 98.9–131% for the three enhanced configurations, with an associated pressure drop penalty increase of 11.3–25.1%, 54.4–72%, and 88.8–121.4%, respectively. An overall performance comparison was conducted by using the London area goodness factor. It is revealed that among the three enhanced configurations, the inline-1RWP case obtains the best overall performance, and the inline-3RWP case is better than the inline-7RWP case. The numerical results were also analyzed on the basis of the field synergy principle to provide fundamental understanding of the relation between local flow structure and heat transfer augmentation. It was confirmed that the reduction in the average intersection angle between the velocity vector and the temperature gradient was one of the essential factors influencing heat transfer enhancement. The analysis also provides guidelines for where the enhancement technique is highly needed.