Reconciling forest preservation and agricultural production is a major challenge. In Brazil, environmental laws have been introduced to reduce forest degradation associated with the expansion of agriculture. However, these laws are constraining small-scale family farmers who rely on cassava produced in shifting cultivation. Faced by scarcity of land, farmers are reducing the fallow periods on their farms. In this study, our hypothesis was that the reduction of the fallow period in shifting cultivation systems leads to a depletion of soil fertility and an increase in weed pressure. In the Brazilian Eastern Amazon region, soil fertility and weed infestation indicators were assessed in 36 cassava fields under shifting cultivation with different land-use histories. The frequency of cultivation of the fields in the past 10 years ranged from 1 to 7 and averaged 3.7 ± 2.3. The results show that the most frequently cultivated fields had lower soil fertility, indicated by lower soil organic carbon, total nitrogen and exchangeable potassium and pH. In addition, labor input for weeding and weeding frequency increased with the frequency of cultivation of the fields, indicating that weed pressure increased with intensified crop cultivation and shorter fallow periods. The findings of this study make clear that the current trend of reducing the fallow period in the Eastern Amazon is a threat to the sustainability and productivity of the local shifting cultivation systems. There is an urgent need for alternative production systems that allow for a better weed control and that contribute to restoring and maintaining soil fertility.