University officials say her departure is not related to the Jerry Sandusky case, during which she served the school.
Penn State general counsel Cynthia Baldwin is leaving two years after establishing the office for the university.
Penn State said the former state Supreme Court justice and university trustee took the job in 2010 in a transitional role to get the office running.
Baldwin said Monday in a statement it was time for the transition. She will help select her permanent replacement.
As the school's attorney, Baldwin served as counsel when two Penn State administrators testified a year ago before a grand jury investigating retired assistant football coach Jerry Sandusky, who faces child sex abuse charges. Sandusky is out on bail and awaiting trial after denying the allegations.
A university spokeswoman tells the Centre Daily Times of State College that Baldwin's departure is unrelated to fallout from the case.
A gubernatorial appointee to Penn State's Board of Trustees, Baldwin served as the board's chairman from 2004 to 2006.
Prior to serving two years as a justice on the state Supreme Court from 2006 to 2008, Baldwin also served more than 16 years as a judge on the Allegheny County Court of Common Pleas.
In a statement two years ago announcing Baldwin's appointment as vice president and chief legal officer, Penn State said the decision to create the in-house legal counsel was based on a recommendation from an external peer review. The school had previously used an outside firm to serve as general counsel.
Separately, Penn State had announced last month that prominent Washington attorney and former White House counsel Lanny Davis would provide legal advice and counsel to school President Rodney Erickson.
The school has said Davis had a different role from Baldwin, whose office advises and coordinates legal matters for the university as a whole. Davis currently heads a law and crisis management firm.