Rice (Oryza sativa L.) is a staple food for more than half of the world's population. To meet the ever-increasing demand for food, because of population growth and improved living standards, world rice production needs to double by 20301. The development of new elite rice varieties with high yield and superior quality is challenging for traditional breeding approaches, and new strategies need to be developed. Here, we report the successful development of new elite varieties by pyramiding major genes that significantly contribute to grain quality and yield from three parents over five years. The new varieties exhibit higher yield potential and better grain quality than their parental varieties and the China's leading super-hybrid rice, Liang-you-pai-jiu (LYP9 or Pei-ai 64S/93-11). Our results demonstrate that rational design is a powerful strategy for meeting the challenges of future crop breeding, particularly in pyramiding multiple complex traits.