Prebys was born in South Bend, Indiana, and graduated from Indiana University. He moved to San Diego in 1965 and co-founded Progress Construction. He bought out his partner in 1980. Over the years, Prebys shifted his focus from construction to property ownership. As of 2015 he owned 81 properties in the greater San Diego area and had an estimated net worth of approximately $1 billion USD.
In December 2004, just prior to Christmas (his favorite time of year); Conrad Prebys made his first philanthropic gift of $1 million to build the Conrad Prebys Clubhouse in Santee and transform the Boys & Girls Clubs of East County into a premier youth-serving organization. His financial support of the organization enabled the organization to grow in quality and scope of Service for the next twenty plus years. Thanks to his largess, more children are coming to state-of-the-art facilities in some of East County's neediest neighborhoods. The result is a population of children who are positively motivated, physically fit and receiving better grades at school.
In the summer of 2014, Prebys donated $25 million to the Salk Institute for Biological Studies, to fund "cutting-edge biological research on a wide range of diseases." His gift was the institute's largest, enabling its researchers to pursue breakthrough medical therapies.