Though he is Roman Catholic, Biden was welcomed as though he were family. He said he thinks of Archbishop Demetrios of America, who introduced the vice president, as a man "radiating compassion" and a close friend.
Biden discussed his ties to the Greek Orthodox community, comically noting that he's been called "Bidenopolis," an honorary Greek name of sorts.
His speech eventually took a more serious turn, focusing on the relationship between the United States and Greece, religious freedom, and the Turkish secessionist state on Cyprus.
The Greek Orthodox Church, Biden said, should be "free to control its destiny" without interference from any government.
He also spent a great deal of time discussing issues resulting from the 1974 Turkish invasion of part of Cyprus, which he said he has been working with others to resolve for years. He called the lack of movement on the issue one of the "great disappointments" of his career.
But he expressed optimism that there would be a fair settlement in the near future. Biden said the parties had finally reached a point where the status quo is not good enough, and finding a compromise would benefit both.
Though there has been much talk about the 2016 Democratic National Convention's possibly being held in Philadelphia - the city has been identified as one of six potential hosts - Biden didn't mention it.
Andrea Mitchell of NBC News, who served as mistress of ceremonies, recalled Biden's history with Philadelphia and Pennsylvania.
"We liked to think of him as Pennsylvania's third senator in those days," said Mitchell, a former Philadelphia radio and TV reporter, referring to the vice president's time as a Delaware senator. Biden is a Scranton native.
Wednesday's visit was Biden's fourth to the state this year. All but one were to Philadelphia, a spokesman said.
One of those visits took place on July Fourth. Biden spoke at Independence Hall as part of the Welcome America! Festival, where he discussed celebrating the freedoms Americans have, specifically citing progress on gay marriage.
On Wednesday, Biden concluded his remarks with a call for compromise among many parties, those on Cyprus among them, but also those closer to home - such as the U.S. government, torn along party lines.
"The American people are better than their leaders now," Biden said. "They deserve better."