Chemical pesticides, regardless of their inherent hazard, are used intensively in the fast changing agricultural sector of Ethiopia. We conducted a cross-sectional pesticide Knowledge, Attitude and Practice (KAP) survey among 601 farmers and farm workers (applicators and re-entry workers) in three farming systems [large-scale closed greenhouses (LSGH), large-scale open farms (LSOF), and small-scale irrigated farms (SSIF)]. Main observations were that 85% of workers did not attain any pesticide-related training, 81% were not aware of modern alternatives for chemical pesticides, 10% used a full set of personal protective equipment, and 62% did not usually bath or shower after work. Among applicators pesticide training attendance was highest in LSGH (35%) and was lowest in SSIF (4%). None of the female re-entry farm workers had received pesticide-related training. Personal protective equipment use was twice as high among pesticide applicators as among re-entry workers (13 versus 7%), while none of the small-scale farm workers used personal protection equipment. Stockpiling and burial of empty pesticide containers and discarding empty pesticide containers in farming fields were reported in both LSOF and by 75% of the farm workers in SSIF. Considerable increment in chemical pesticide usage intensity, illegitimate usages of DDT and Endosulfan on food crops and direct import of pesticides without the formal Ethiopian registration process were also indicated. These results point out a general lack of training and knowledge regarding the safe use of pesticides in all farming systems but especially among small-scale farmers. This in combination with the increase in chemical pesticide usage in the past decade likely results in occupational and environmental health risks. Improved KAP that account for institutional difference among various farming systems and enforcement of regulatory measures including the available occupational and environmental proclamations in Ethiopia are urgently needed.