The mission statement of Zeta Psi is:

Zeta Psi strives to be a premier international men's fraternal organization dedicated to forging academic excellence and life-long bonds of brotherhood. Through active chapter participation and continuing alumni involvement, Zeta Psi members are committed to the development of leadership, character and intellect to the service of their brothers, their communities and mankind.

Its international headquarters is located in Pearl River, New York. Its current president is M. Lauck Walton, who was elected in 2010.

On the first of June in 1847, three young men gathered in a New York City bungalow with a purpose in mind: the constitution of a new Greek-letter society. Their names were John Bradt Yates Sommers, William Henry Dayton, and John Moon Skillman.

Then students at New York University (itself a young campus, only founded in 1831), the three men formed the core of the first chapter, Phi. But William Dayton was stricken with poor health, and departed New York shortly afterwards for more temperate climes. He retired to the University of North Carolina at Chapel Hill, where the warm weather and liberal policies were expected to improve his humors, intending to begin a chapter there. But the move was inauspicious: Dayton died within the year, and the University of North Carolina was without a chapter of Zeta Psi for over a decade.

The Phi chapter at NYU persisted in his absence, and graduated its first member the next year with George S Woodhull (Φ '48). The second chapter was established as Zeta at Williams College in Massachusetts. The Delta chapter was founded at Rutgers University later that year, and remains the most longevous continuously active chapter of the fraternity (the Phi chapter was briefly inactive in the 1970s).

Three chapters followed in 1850: Omicron (now Omicron Epsilon) at Princeton University, Sigma at the University of Pennsylvania, and Chi at Colby College in Waterville, Maine. The first two are still active, as was the Chi Chapter until 1988. But in the early 1980s Colby College prohibited Fraternities on campus, despite the long and storied tradition they had enjoyed there. By 1988, ejected from campus and banned from any formal rush, the chapter quietly expired after over 130 years of existence. Problems beset other early chapters as well. The first Alpha chapter was founded in 1852 at Dickinson College in Carlisle, Pennsylvania. But immediate resistance from the administration slowly wore upon the brothers there, and that chapter became inactive in 1872, permitting its letter to be used for the later chapter founded at Columbia.

But expansion proceeded apace throughout the 1850s at a rate of several chapters per year: Epsilon was chartered at Brown University and Rho (later re-chartered as Rho Epsilon) at Harvard University in 1852; Psi (later re-chartered as Psi Epsilon) at Dartmouth College in 1853; Kappa at Tufts University in 1855; Theta at Union College in 1856; Tau at Lafayette College in 1857; Xi at University of Michigan in 1858. Also in 1858, the Upsilon chapter was finally founded at the University of North Carolina, fulfilling the purpose of Brother Dayton in his last journey south. And in that year an abortive attempt was made to colonize Amherst College with the Pi chapter, which was rechartered at Rensselaer Polytechnic Institute in 1865 as the war among the several states loomed large.

Abraham Lincoln was elected president of the United States in 1860, and South Carolina seceded from the Union, followed shortly thereafter by her fellow Southern states. Expansion of the Fraternity halted as campuses rallied for war and sent companies of their collegemen to battle.

At the outbreak of war, the Upsilon chapter at UNC— only chartered three years before—found itself the only chapter of Zeta Psi among all the Southern states, sundered from the North by the sudden lines of enmity. But even as they mustered for war and marched south, the Grand Chapter of Zeta Psi, specially assembled in early July 1862, adopted the resolution of Brother William Cooke (Φ '58) prescribing unity: