The school announced Tuesday that Specter, 80, will join as an adjunct faculty member in the fall.
His course will focus on the separation of powers and the Supreme Court confirmation process, something he was involved with as a member of the Senate Judiciary Committee from 1981 to 2010, including as its chairman from 2005-07.
"Arlen's knowledge of the inner workings of the government and lawmaking is second to none," said Michael A. Fitts, the law school's dean. "The insight he brings from his career in public service, particularly as a leader on judicial issues, will be invaluable to our students as they prepare for their own careers in the law."
Specter was perhaps best-known for his role in Supreme Court confirmations - he took part in 14 hearings, he said - because of his long service on the Judiciary Committee and his dogged questioning.
Often, he sought a nominee's assurances that they would give proper weight to legal precedent - the body of law developed through more than a century of Supreme Court decisions.
He helped sink Reagan's 1987 nomination of Robert H. Bork, calling him a "throwback" who would help outlaw abortion.
And in 1991, he earned the enduring anger of many Democrats - and a tough re-election challenge a year later - when he aggressively questioned the honesty of Anita Hill, a law professor who had accused Supreme Court nominee Clarence Thomas of sexual harassment.
"I'm excited to join a vibrant academic community that's on the cutting edge of today's most important legal issues," Specter said in a statement. "As I transition to a new phase of my career, teaching at Penn Law will be a fantastic opportunity to join an outstanding community of scholars, continue my work in public policy and the law, and impact the next generation of lawyers and policy makers."
Specter graduated from the University of Pennsylvania. After earning a law degree at Yale University, he began his public service in 1959 as an assistant city district attorney in Philadelphia.
He was the state's longest serving senator and a Republican for most of those years but switched to the Democratic Party. He lost in last year's Democratic primary to then-U.S. Rep. Joe Sestak, who ultimately lost to Republican Pat Toomey.
Associated Press writer Marc Levy in Harrisburg, Pa., contributed to this report.