Characterization and analysis of the relationship between cropping practices, pest constraints, and yield variation in Cambodia are necessary for developing sustainable crop and pest management strategies as agriculture intensifies. Rice production is transforming from subsistence to a market-oriented, intensive system. Field surveys were conducted during the wet season (May to December) of 2016 in two districts of each of the four main rice-growing provinces. The intensity of injuries caused by pests (diseases, insect pests, rodents and weeds) and yield were assessed in farmers’ fields. Data on cropping practices were obtained through structured interviews of farmers who managed the surveyed fields. The average yield was 4.03 t ha−1, which was threefold higher than the yield obtained in 1990. Comparison of results with those obtained from surveys in the 1990s indicates a substantial increase in the proportion of direct-seeded fields, reliance of farmers on pesticides, and seeding and nutrient rates. PCA and correlation analyses showed that these cropping practices favored the occurrence of rodents, brown spot, and weeds, which were most closely associated with low yield. Correspondence analysis identified three groups of fields with varying levels of intensification, pest profiles, and yield levels. Cropping intensification was highest in areas where IR50401-77-2-1-3, a modern variety, was grown and lowest in areas where Phka Rumdoul, a traditional variety, was transplanted. Farmers managed pests by relying on pesticides and increasing the seeding rate. In general, increasing agricultural inputs did not affect the intensity of pest injuries, or increase yield, indicating that these can be reduced or optimized without compromising yield and pest management efficiency. To reduce reliance of farmers on pesticides as the main strategy for pest management and promote sustainable rice production, there is a need to create an enabling environment for the adoption of ecologically based pest management approaches and provide economic incentives, such as certification of rice grown under sustainable production standards and linking farmers with market networks for sustainably grown rice.