Bread wheat is one of the most important cereals in the highlands of Uganda, and is grown mainly under rainfed conditions by subsistence farmers. The national mean wheat grain yield is less than 1.5 t/ha. Weed infestation is one of the factors causing significant yield losses. The farmers’ practice of controlling the weeds through use of selective herbicide 2,4-D and hand pulling of the weeds has led to the proliferation of noxious grassy weeds in this region. The study was conducted to assess the effectiveness of different herbicide combinations for controlling of both broad leaved and grassy weeds in wheat. The experiment was laid out in a RCBD with four replicates and the treatments comprised of application of four different herbicides singly and in different combinations as tank mix. The study was conducted for two seasons in 2017 season A&B and the results showed significant differences among treatments. A single application of a combination of ralon super and buctril at three leaf stage reduced both broad leafed and grassy weeds by more than 90%. This led to an increase in yield of more than 2.5 t/ha and an increased cost–benefit ratio. Post-emergence combination of both grass and broad leaf herbicides were found to be both economical for wheat production and effective in releasing labor for other farm operations. With the introduction of new varieties, the technology will serve to boost yield and increase net farm incomes.