In order to develop a sustainability index (SI) for quantifying the sustainability of a wheat-cotton agroecosystem, a study was conducted in 2003 in the KHORASSAN province. Data of socio-economic, agronomic and ecological indicators were collected using 518 questionnaires. Results showed that only 18.6 percent of farmers gained the half or more of SI scores. The mean SI score was 44.0 which indicate that these agro ecosystems are not sustainable. Results of this study are in consistent with other reports in other regions of the country. Livestock production, crop production, and water and irrigation indicators had the lowest score (6, 31, and 37, respectively). The backward stepwise regression analysis indicated that SI can be predicted from a linear combination of field size, wheat yield, crop residue management, crop income and education and extension services, while application of chemical fertilizers did not add to the prediction ability of SI. Results also showed that any progress in farmers' education, economic viability, crop production management and water use efficiency could improve overall sustainability of these agroecosystems substantially.