Witnesses say a group of about 20 people suddenly gathered outside the building's main foyer at 5th Street and Grand Avenue and started hammering at the plate-glass windows.
Others used paint to scrawl messages such as "burn all banks" and "credit scores suck."
A front door was shattered and most of the huge plate-glass windows lining the lobby were fractured and will have to be replaced.
Police say the group had scattered by the time officers arrived and no arrests have been made.
Investigators are looking at surveillance video to help in the search for suspects.
The 73-story U.S. Bank Tower, built in 1989, is the third-tallest building on the West Coast. U.S. Bank does not own the building, but is one of the major tenants.