The Thomas P. O'Neill Jr. House Office Building is the fifth office building now occupied by the U.S. House of Representatives.

The O'Neill Building is located southwest of the Capitol on city Square 579 and is bounded by Second Street, C Street, Third Street, and D Street SW. It is the second O'Neill Building occupied by the House; a former hotel acquired by Congress in 1957 was named for O'Neill in 1990. The earlier O'Neill Building was replaced by a parking lot in 2002.

The current O'Neill Building opened as Federal Office Building No. 8 in 1965 and served as laboratory space for the Food and Drug Administration. Naramore, Bain, Brady & Johanson designed the utilitarian building with a mostly limestone façade. It was one of the few federal buildings completed during the presidency of John F. Kennedy; his name appears on the cornerstone.

In 2008, the building was gutted, and construction on the redesign began in 2010. The O'Neill Building reopened for federal agency occupancy in 2014. Legislation transferred ownership of the 548,345-square-foot facility from the General Services Administration to the U.S. House of Representatives in June 2017. The building is occupied by 2000 employees of various committees of the U.S. House of Representatives, the Clerk of the House, legislative support organizations, and the U.S. Department of Health and Human Services.

The modernized facility now includes open-plan, flexible office space and a green roof, and the renovations greatly increased the natural light entering the building. Building systems were re-engineered and upgraded. The majority of the original limestone wall panels on the east and west sides were replaced with glass curtain walls, and the existing windows on the north and south sides were replaced with full-height glass curtain walls. The limestone was reused on the project, one example of the sustainability practices incorporated in the renovation work. A seven-story central atrium with skylight was added, and a six-story entrance atrium with skylight now graces the north side of the building. At the main entry, the glass wall provides views of the U.S. Capitol; it evokes the lines and massing of a waterfall and anchors a pedestrian plaza where a parking lot once stood. Despite these changes, 95% of the original structure remained intact during construction. These renovations helped the building earn a Leadership in Engineering and Environmental Design (LEED) Platinum certification.

Public Law 112-237, approved on December 28, 2012, named the facility the Thomas P. O'Neill Jr. Federal Building. The legislation that transferred ownership of the building to the House, Public Law 114-254 (approved December 10, 2016), renamed it the Thomas P. O'Neill Jr. House Building. "Tip" O'Neill, a Democrat from Massachusetts, served as Speaker of the House from 1977 to 1987.