Pierre L'Enfant's 1792 plan for the federal city specified a site for a "great church for national purposes," though the idea lay dormant for a century. In 1893, Congress granted a charter to the Protestant Episcopal Cathedral Foundation to establish a cathedral in Washington. The site chosen was Mount Saint Alban, the highest point in the District of Columbia. On September 29, 1907, President Theodore Roosevelt addressed a crowd of more than 20,000 as the foundation stone was laid. Bethlehem Chapel opened for daily services in the unfinished structure in 1912, and those services have continued without interruption ever since. Both original architects, the British Gothic master George Frederick Bodley and his partner Henry Vaughan, died before the building was well underway. American architect Philip Hubert Frohman, who had designed his first functional home at age fourteen and earned his architecture degree at sixteen, took over the design and devoted the rest of his life to it. The "final finial" was placed on September 29, 1990, in the presence of President George H. W. Bush, exactly 83 years to the day after Roosevelt laid the cornerstone.

The cathedral's planners hoped it would serve as America's Westminster Abbey, and it has. State funerals for five presidents have taken place within its nave: Dwight D. Eisenhower in 1969, Ronald Reagan in 2004, Gerald Ford in 2007, George H. W. Bush in 2018, and Jimmy Carter in 2025. The roster of memorial services reads like a history of American public life: Supreme Court Justice Thurgood Marshall, astronaut Neil Armstrong, civil rights leader Dorothy Height, Senator John McCain, Secretary of State Colin Powell, Justice Sandra Day O'Connor, Secretary of State Madeleine Albright. After the September 11 attacks, the nation's leaders convened here for a memorial service. The cathedral has also hosted inauguration prayer services for presidents from both parties, from Franklin Roosevelt's second inauguration in 1937 through Donald Trump's second inauguration in 2025. In the words of historian Jon Meacham, speaking of the Canterbury Pulpit carved from stones taken from Canterbury Cathedral itself, "it is from here, from this rock, that preachers are given the peculiar opportunity to address not only those in the pews but those in power."

The cathedral is the second-largest church building in the United States and the third-tallest structure in Washington, D.C. Its Neo-Gothic design draws on the English Gothic style of the late fourteenth century, with pointed arches, flying buttresses, and over two hundred stained glass windows. The Gloria in Excelsis Tower rises above the crossing, and its summit is the highest point in the entire District. The architects designed the crypt chapels in Norman, Romanesque, and Transitional styles predating the Gothic, as though the cathedral had been built atop the ruins of earlier churches, a deliberate echo of European cathedral tradition. The building contains intentional "flaws," following an apocryphal medieval custom meant to demonstrate that only God can be perfect. The west rose window, designed by Rowan LeCompte, is an abstract depiction of the creation of light. LeCompte chose a nonrepresentational design because he feared that a figural window would be unreadable from the vast distance to the nave. The west facade, sculpted by Frederick Hart, follows a program of Creation rather than the Last Judgment, making it unusual among Gothic cathedrals.

In 1953, stained glass windows honoring Confederate generals Robert E. Lee and Stonewall Jackson were installed in the cathedral after lobbying by the United Daughters of the Confederacy. For decades they remained, Confederate battle flags rendered in colored light inside a house of worship. In 2016, a task force examined the windows and unanimously concluded they provided "a catalyst for honest discussions about race and the legacy of slavery." In September 2017, the cathedral's leadership announced the windows would be deconsecrated and removed. The Robert E. Lee window was loaned to the Smithsonian's National Museum of African American History and Culture. In their place, on September 23, 2023, the "Now and Forever" windows were unveiled, designed by artist Kerry James Marshall, with a dedication featuring a reading of "American Song" by poet Elizabeth Alexander. The cathedral's willingness to remove and replace its own sacred art marked a rare public reckoning with the compromises built into American institutions.

Woodrow Wilson is the only American president buried in Washington, D.C., and his tomb lies in the cathedral's nave. His wife Edith is interred beside him. But Wilson is far from alone. Helen Keller's ashes rest here, alongside those of her teacher and companion Anne Sullivan, who was the first woman interred in the cathedral. Admiral George Dewey, hero of Manila Bay, lies in the crypt. Three Nobel Peace Prize laureates are buried on the grounds: Secretary of State Cordell Hull, Secretary of State Frank B. Kellogg, and YMCA leader John Raleigh Mott. In 2018, the ashes of Matthew Shepard, the young gay man whose 1998 murder became a landmark in the fight for LGBTQ rights, were interred at the cathedral in a Service of Thanksgiving and Remembrance. The cathedral's columbarium and burial spaces hold diplomats, fighter pilots, composers, and bishops, a cross-section of American ambition and service stretching back more than a century.