The world's most traveled spaceship took off from Cape Canaveral, Fla., and later landed at Dulles International Airport, just outside Washington, D.C.
The shuttle, and the 747 it was on, made a series of ceremonial flyovers before touching down. Thousands of people lined the National Mall between the Washington Monument and the Capitol to get a view of the shuttle as it circled three times through partly cloudy skies.
On Thursday, Discovery will be towed to its installation at the Smithsonian's National Air and Space Museum in northern Virginia.
NASA ended the shuttle program last summer after a 30-year run to focus on destinations beyond low-Earth orbit. During its tenure, the spaceship clocked almost 149 million miles.
The Associated Press contributed to this report.