Per capita food production has declined in Kenya — largely as a result of high population growth and rapid land depletion. Recent trends suggest that food insecurity will persist in Kenya as the natural resource base for agriculture continues to be depleted, as evidenced by the widespread negative nutrient balances for most smallholder agriculture. These negative nutrient balances arise as a result of an imbalance between nutrient inputs and harvest removal, erosion and leaching. Using maize yields as an indicator, farms in this region exhibit contrasting soil fertility degradation levels based on the time of land conversion from primary forest to agriculture. We evaluated the impact of soil fertility amendments: manure, green manure (Tithonia diversifolia), and inorganic N (nitrogen) and P (phosphorus), on maize yield on farms at various levels of soil fertility degradation in this region for two cropping seasons (long and short rain seasons) in the western highlands of Kenya. Three blocks, seven times periods (representing age of cultivation) and three farms (representing replicates per block) per time period were used. Maize responded differently along the chronosequence of soil fertility degradation when either organic and inorganic fertilizers were applied to supply N and P. Maize grain yield ranged between 1.03 and 8 metric tons per hectare for the two seasons. Highest impact of both N and P was observed on the oldest conversions. Maximum crop response for P was observed at 25 kg P per hectare under high N (100 kg N per hectare). Effectiveness of manure (25 kg P per hectare) was improved with the addition of 100 kg N per hectare especially on the old conversions. The implications of our results for understanding the dynamics of soil fertility degradation, the impact of soil fertility management, and the challenges of soil fertility restoration on smallholder farms in the highlands of Kenya are discussed.