Australia has one of the oldest modern wheat breeding programs worldwide although the crop was first introduced to the country in 1788. Breeders selected wheat with high adaptation to different Australian climates, while ensuring satisfactory yield and quality. This artificial selection left distinct genomic signatures that can be used to retrospectively understand breeding targets, and to detect economically important alleles. To study the effect of artificial selection on modern cultivars and cultivars released in different Australian states, we genotyped 482 Australian cultivars representing the history of wheat breeding in Australia since 1840. Computer simulation showed that 86 genomic regions were significantly affected by artificial selection. Characterization of 18 major genes known to affect wheat adaptation, yield, and quality revealed that many were affected by artificial selection and contained within regions under selection. Similarly, many reported QTL and genes for yield, quality, and adaptation were also contained in regions affected by artificial selection. These included TaCwi-A1, TaGw2-6A, Sus-2B, TaSus1-7A, TaSAP1-7A, Glu-A1, Glu-B1, Glu-B3, PinA, PinB, Ppo-D1, Psy-A1, Psy-A2, Rht-A1, Rht-B1, Ppd-D1, Vrn-A1, Vrn-B1, and Cre8. Interestingly, 17 regions affected by artificial selection were in moderate-to-high linkage disequilibrium with each other with an average r2 value of 0.35 indicating strong simultaneous selection on specific alleles. These regions included Glu-B1, TaGw2-6A, Cre8, Ppd-D1, Rht-B1, Vrn-B1, TaSus1-7A, TaSAP1-7A, and Psy-A1 plus multiple QTL affecting wheat yield and yield components. These results highlighted the effects of the long-term artificial selection on Australian wheat germplasm and identified putative regions underlying important traits in wheat.