Farmers in the mid-hills of Nepal have a mix of rainfed land on which millet is grown in relay after maize (maize/millet), and irrigated land on which wheat is grown sequentially after rice (wheat–rice). Double cropping is the norm but the diminishing quantities of organic materials, coupled with the trend towards increased use of inorganic fertilizers, have raised questions about the long-term productivity and sustainability of the cropping systems. The aim of this work was to examine the long-term effects (eight years) on grain yield of additions of manure and fertilizer either singly or in combination. Maize/millet and wheat–rice rotations were established on a Dystochrept at Pakhribas Agricultural Centre at about 1450 m altitude. Manure and fertilizer applications were applied to the maize (eight combinations in May) and the wheat (different rates in seven combinations in November) every year with the succeeding crops (millet and rice) utilizing residual nutrients. Yields of maize, millet and rice were greater when manure rather than fertilizer was applied but yields of wheat were less. The combined application of manure and fertilizer significantly increased yields of maize and wheat compared with applications of either manure or fertilizer alone. However, for the subsequent crops (millet and rice) there was either a small residual benefit of the combined application when compared with fertilizer alone, or no benefit when compared with manure alone. Overall, the combined application increased total grain yields by about 35% in the maize/millet rotation and by 16% in the wheat–rice rotation. There was no trend in yields in response to treatment with time.