About 30 pro-immigration demonstrators made it into the building before police arrived and blocked the entrance on Market Street, near 16th Street.
They included families of people who were deported during the Obama administration.
They occupied the lobby for less than an hour before being dispersed by police. Six of them were arrested.
"We want to confront Joe Biden. Under his administration, about 3 million people got deported. A lot of families got separated under his administration with Obama," said Carlos Castaneda, a spokesman for the group.
There's no sign that Biden was in the building and his campaign did not respond to a request for comment. But the mere fact his headquarters is there could make the building a protest magnet. Sen. Pat Toomey's office, for instance, attracts weekly demonstrations.
Philadelphia police say they have no special plans for guarding the building and will "make response and deployment decisions as conditions dictate." There are, however, lots of bicycle officers in the area regularly.