Wheat is an economically important food crop in South Africa and is affected by a number of fungal diseases, especially leaf-, stem- and stripe rust as well as Fusarium head blight (FHB). The aim of the study was to stack diverse rust and FHB resistance sources into a single locally adapted spring wheat line using different breeding schemes as well as phenotypic and molecular screening methods. Wheat lines with resistance to the three rusts and FHB were successfully developed using parental lines that contained the following rust and FHB resistance genes/quantitative trait loci (QTL): Lr19, Lr34/Yr18/Sr57, Sr2, Sr26, Sr39, YrSp, QYr.sgi-2B.1, Fhb1 and Fhb5. Foreground marker-assisted selection was employed to follow introgression of targeted genes/QTL for development of double-cross, self-pollinated and doubled haploid (DH) populations. Best lines were furthermore evaluated and selected using phenotypic rust and FHB resistance evaluation in the greenhouse and under field conditions as well as by quantifying biomass accumulation of the inoculated pathogen in each line using reverse transcriptase real-time polymerase chain reaction (RT-qPCR) analysis. RT-qPCR results correlated with infection type scores and the combination of genes/QTL present. Lines containing all nine rust and FHB genes/QTL were identified. Two of the interspecific (wheat x maize) crosses produced promising DH lines containing six and seven resistance genes/QTL, respectively. Wheat lines developed in this study will contribute towards breeding and release of cultivars with more complex and thereby hopefully more durable sources of rust and FHB resistance.