Climate models have consistently projected a drying trend in the southwestern United States, aiding speculation of increasing dust storms in this region. Long-term climatology is essential to documenting the dust trend and its response to climate variability. We have reconstructed long-term dust climatology in the western United States, based on a comprehensive dust identification method and continuous aerosol observations from the Interagency Monitoring of Protected Visual Environments (IMPROVE) network. We report here direct evidence of rapid intensification of dust storm activity over American deserts in the past decades (1988-2011), in contrast to reported decreasing trends in Asia and Africa. The frequency of windblown dust storms has increased 240% from 1990s to 2000s. This dust trend is associated with large-scale variations of sea surface temperature in the Pacific Ocean, with the strongest correlation with the Pacific Decadal Oscillation. We further investigate the relationship between dust and Valley fever, a fast-rising infectious disease caused by inhaling soil-dwelling fungus (Coccidioides immitis and C. posadasii) in the southwestern United States. The frequency of dust storms is found to be correlated with Valley fever incidences, with a coefficient (r) comparable to or stronger than that with other factors believed to control the disease in two endemic centers (Maricopa and Pima County, Arizona). Plain Language Summary Computer models predict that as the Earth warms, the Southwest United States will become drier. In the already arid Southwest, this means more dust storms and even potential environmental catastrophes such as desertification and another Dust Bowl. Using a newly reconstructed data record, we found that indeed this region is seeing more dust storms in the past decades. There was a 240% increase in the number of large dust storms between 1990s and 2000s. The sharp increase of dust storms is likely driven by tiny changes of sea surface temperature in the northern Pacific Ocean. In the Southwest frequented by dust storms, the infection rate of Valley fever has mysteriously gone up more than 800% from 2000 to 2011. Little is known about what drives the fast rise, although a number of factors are found moderately correlated to the outbreaks. In two endemic centers, dust storms are found to better correlated with the disease than any other known controlling factor. This work implied a potential teleconnection between large-scale climate variations and infectious disease in sensitive regions, although future work is needed to confirm the linkages.