The Pennsylvania Beta Chapter of Phi Kappa Psi was founded on May 8, 1855 by Thomas Ruskin Kennedy. It was the fourth chapter of Phi Kappa Psi to be chartered. Pennsylvania Beta has existed for 150 years without interruption or suspension of its charter, making it the oldest, uninterrupted chapter of Phi Kappa Psi, and indeed of any intercollegiate fraternity. Throughout the chapter's history, Pennsylvania Beta has initiated some of Phi Kappa Psi's most influential alumni. William Clayton Wilson, who was initiated into Pennsylvania Beta in 1875, planned a new form of government and drafted a new constitution for Phi Kappa Psi that is, for the most part, still used today. Since its inception, Pennsylvania Beta has intitiated over 1,800 men.

Pennsylvania Beta's first chapter house was built in 1905 and was located on the corner of North Main Street and East College Street at what is now the site of Pelletier Library. This was the first fraternity house on Allegheny College's campus and one of the first fraternity houses in the country. The fraternity house was removed in 1970 and relocated to Highland Street. The Pennsylvania Beta Brothers remained there until 1995 when the fraternity house was removed to make room for the Wise Sports and Fitness Center. The fraternity house is currently located on the corner of East College Street and Highland Street.