Head rice yield (HRY) is a crucial quality trait that determines the final commodity yield and commercial value of rice. Conversely, chalkiness represents an undesirable appearance characteristic, significantly impairing rice marketability. Thus, developing rice germplasms with superior HRY and appearance traits is highly desirable for rice production and marketing. However, the master modules and regulatory networks underlying HRY and chalkiness remain largely unknown. Here, we demonstrate that the rice transcription factor OsMYB99 acts as a master regulator conferring high HRY and low chalkiness. Functional loss of OsMYB99 impairs cuticular wax biosynthesis and deposition in caryopses and causes accumulation of reactive oxygen species (ROS) in endosperms, consequently decreasing HRY and increasing chalkiness. Mechanistically, OsMYB99 functions as a transcription activator; it binds promoters and positively regulates the expression of wax biosynthesis gene OsGL1-4 and ROS scavenger OsMT2b. OsGL1-4 promotes cuticular wax biosynthesis and deposition in caryopses, while OsMT2b eliminates excess ROS in endosperms. Together, these actions lead to HRY enhancement and chalkiness reduction. Our study uncovers the master regulator OsMYB99 and its molecular network modulating HRY and chalkiness in rice, offering a strategy to improve these traits through modifying cuticular wax deposition and ROS production.