In order to support agribusiness and to attain food security for ever-increasing populations, most countries in the world have embraced modern agricultural technologies. Ecological consequences of the technocentric approaches, and their sustainability and impacts on human health have, however, not received adequate attention particularly in developing countries. India is one country that has undergone a rapid transformation in the field of agriculture by adopting strategies of the Green Revolution. This article provides a comparative analysis of the effects of older and newer paradigms of agricultural practices on ecosystem and human health within the larger context of sustainability. The study was conducted in three closely situated areas where different agricultural practices were followed: (a) the head-end of a modern canal-irrigated area, (b) an adjacent dryland, and (c) an area (the ancient area) that has been provided with irrigation for some 800 years. Data were collected by in-depth interviews of individual farmers, focus-group discussions, participatory observations, and from secondary sources. The dryland, receiving limited rainfall, continues to practice diverse cropping centered to a large extent on traditional coarse cereals and uses only small amounts of chemical inputs. On the other hand, modern agriculture in the head-end emphasizes continuous cropping of rice supported by extensive and indiscriminate use of agrochemicals. Market forces have, to a significant degree, influenced the ancient area to abandon much of its early practices of organic farming and to take up aspects of modern agricultural practice. Rice cultivation in the irrigated parts has changed the local landscape and vegetation and has augmented the mosquito population, which is a potential vector for malaria, Japanese encephalitis and other diseases. Nevertheless, despite these problems, perceptions of adverse environmental effects are lowest in the heavily irrigated area.