The O'Shaughnessy brothers' story takes place between 1860 and 1950 in Illinois, Missouri, New York, and Ireland. They were the children of an impoverished immigrant who fled the famine in Ireland and of his Irish-American wife. An Irish-American Odyssey is the tale of this first generation immigrant family's struggle to assimilate into American society, highlighting their perseverance and determination to seize opportunities and surmount obstacles, all the while establishing a legacy for their own descendants in American art, advertising, journalism, and public service.

TIME magazine called James O'Shaughnessy the best in the business of advertising, and he became the first chief executive of the American Association of Advertising Agencies. Earlier, he was a star reporter at the Chicago Tribune, and James and Francis were centrally involved in founding and maintaining the Irish Fellowship Club. Francis was also the first graduate of the University of Notre Dame to be invited to deliver its annual commencement address, while Martin was the first captain of Notre Dame's official basketball team. An attorney, John represented the alleged victim in a notorious white slavery case. Thomas (Gus) became the leading Gaelic Revival artist in America as well as a promoter of Italian-American heritage, campaigning successfully to have Columbus Day enacted a public holiday.

The remarkable rise of the O'Shaughnessy brothers proves the American dream is attainable.