Soil acidification is a serious constraint to food production worldwide. This review explores its primary causes, with a focus on the role of nitrogen fertilizer, and suggests mitigation strategies based on optimal N management. Natural acidification is determined by the leaching of weak acid mainly caused by climate and soil conditions, whereas the use of ammonium-based fertilizers, nitrate leaching and removal of base cations (BCs) by crop harvesting mostly accounts for anthropogenic acidification. In addition, low soil acid buffering capacity, mainly determined by soil parent materials and soil organic matter content, also accelerates acidification. This study proposes targeted mitigation strategies for different stages of soil acidification, which include monitoring soil carbonate content and pH of soils with pH > 6.5 (e.g., calcareous soil), use of alkaline amendments for strongly acidic soils (pH < 5.5) with aluminum toxicity risk to pH between 5.5 and 6.5, and decreasing acidification rates and supplementing BCs to maintain this optimal pH range, especially for soils with low acid buffering capacity. Effective mitigation involves optimizing the rate and form of N fertilizers used, regulating N transformation processes, and establishing an integrated soil–crop management system that balances acid production and soil buffering capacity.