Smallholder farmers in the Guinea savanna practise cereal-legume intercropping to mitigate risks of crop failure in mono-cropping. The productivity of cereal-legume intercrops could be influenced by the spatial arrangement of the intercrops and the soil fertility status. Knowledge on the effect of soil fertility status on intercrop productivity is generally lacking in the Guinea savanna despite the wide variability in soil fertility status in farmers’ fields, and the productivity of within-row spatial arrangement of intercrops relative to the distinct-row systems under on-farm conditions has not been studied in the region. We studied effects of maize-legume spatial intercropping patterns and soil fertility status on resource use efficiency, crop productivity and economic profitability under on-farm conditions in the Guinea savanna. Treatments consisted of maize-legume intercropped within-row, 1 row of maize alternated with one row of legume, 2 rows of maize alternated with 2 rows of legume, a sole maize crop and a sole legume crop. These were assessed in the southern Guinea savanna (SGS) and the northern Guinea savanna (NGS) of northern Ghana for two seasons using three fields differing in soil fertility in each agro-ecological zone. Each treatment received 25 kg P and 30 kg K ha-1 at sowing, while maize received 25 kg (intercrop) or 50 kg (sole) N ha-1 at 3 and 6 weeks after sowing. The experiment was conducted in a randomised complete block design with each block of treatments replicated four times per fertility level at each site. Better soil conditions and rainfall in the SGS resulted in 48, 38 and 9% more maize, soybean and groundnut grain yield, respectively produced than in the NGS, while 11% more cowpea grain yield was produced in the NGS. Sole crops of maize and legumes produced significantly more grain yield per unit area than the respective intercrops of maize and legumes. Land equivalent ratios (LERs) of all intercrop patterns were greater than unity indicating more efficient and productive use of environmental resources by intercrops. Sole legumes intercepted more radiation than sole maize, while the interception by intercrops was in between that of sole legumes and sole maize. The intercrop however converted the intercepted radiation more efficiently into grain yield than the sole crops. Economic returns were greater for intercrops than for either sole crop. The within-row intercrop pattern was the most productive and lucrative system. Larger grain yields in the SGS and in fertile fields led to greater economic returns. However, intercropping systems in poorly fertile fields and in the NGS recorded greater LERs (1.16 – 1.81) compared with fertile fields (1.07 – 1.54) and with the SGS. This suggests that intercropping is more beneficial in less fertile fields and in more marginal environments such as the NGS. Cowpea and groundnut performed better than soybean when intercropped with maize, though the larger absolute grain yields of soybean resulted in larger net benefits.