Mineral fertiliser is a scarce input for smallholder maize farmers in Malawi. A recent provision of small amounts of subsidised fertilisers by government programmes to farmers throughout Malawi has increased fertiliser access and raised maize production, but fertiliser management and yield responses frequently remain poor. To seek ways to use the fertiliser more efficiently, we analysed the effects of low rates of N (15 or 30 kg N ha−1) and P (9 kg P ha−1) fertiliser in combination with improved weed management on maize yields in experiments on 12 smallholder farms in Chisepo, central Malawi. Several indices of N and P use efficiency were computed from the above-ground crop components and nutrient contents. Maize yield simulations were conducted using long-term rainfall records in the APSIM crop-soil system model. NP fertiliser significantly (p < 0.001) raised maize grain yield from 0.65 to 1.5 t ha−1, and twice-weeding fertilised maize significantly (p < 0.001) raised maize yields by 0.4 t ha−1 compared with weeding once (0.9 t ha−1). The agronomic efficiency of applied fertiliser N (AEN) averaged 19.3 kg grain kg N−1 with one weeding but doubled to 38.7 kg with the additional weeding. The physiological efficiency of applied N (PEN) was 40.7 kg grain kg−1 N uptake. APSIM predicted that similar or larger maize yield responses to 15 or 30 kg N ha−1 can be expected in 8 out of 10 years in areas with similar rainfall patterns to Chisepo. A financial analysis showed that the application of these small amounts of fertiliser was economic even when fertiliser was purchased from the open market, provided the crop was adequately weeded. Participatory assessments helped farmers understand the increased efficiency of fertiliser use possible with additional weeding, although some farmers reported difficulty implementing this recommendation due to competing demands for labour. We conclude that to raise the productivity and sustainability of fertiliser support programmes in Malawi, initiatives should be introduced to help identify and educate farmers on the major drivers of productivity in their systems.