Officials at the Ivy League school in Philadelphia say Biden will speak at commencement on May 13.
Biden has many connections to Penn. His granddaughter is a freshman and his son Beau, the attorney general of Delaware, is an alum.
Biden also spoke at the 2010 graduation for Penn's School of Social Policy and Practice, when his daughter Ashley received a master's degree.
On Tuesday, Penn announced that Biden will be among nine people to receive honorary degrees at the spring ceremony.
Other honorees include former Chile president Michelle Bachelet, who now runs the United Nations women's agency, and Xerox CEO Ursula Burns, the first African-American woman to lead a Fortune 500 company.
