Common farming practices in intensive agriculture can be serious causes of water quality degradation, depending on the interaction between physical vulnerability of the farmland and farmers’ behaviors in practicing farming. However, relevant information is highly limited in Greece. Farmers’ attitudes and practices in the use of chemical fertilizers, pesticides, and irrigation water were explored in Serres region in northern Greece to understand behavior in practicing farming. The majority of the farmers considered that chemical fertilizers are harmful substances particularly to surface and groundwater and pesticides are highly harmful to human health. Most farmers showed high levels of awareness of the potential impact of farming practices on the environment, probably due to a combination of high experience in farming, adequate formal education, and valid sources of information. Farmers’ compliance with most recommended practices showed high understanding of most components of conservation practices in fertilization, except from a void in the use of soil tests for better adjustment of the fertilization and in the use of organic fertilizers. Only a small fraction of farmers (4.4 %) were found to overuse fertilization, more often in sandy soils, but this practice was not accompanied by excessive use of irrigation water. As for pesticide use, farmers’ compliance with most recommended practices showed high levels of rational use, except from the management of empty pesticide containers. None of the farmers overused soil pesticides with reference to application rates and frequency. Data provide key information for natural resource managers, relevant stakeholders, and local authorities to understand how farmers view their relationship to farming as well as how farmers practice farming. The collected evidence can serve as a valuable benchmark for future comparisons in Greece and possibly for comparisons with other areas of southern Europe. Tailored education programs that improve farmers’ knowledge in fertilizing, pesticide use, and their impact on the environment can be a major step towards promoting sustainable farming and reducing potential environmental contamination.