The X-37B is expected to land at Vandenberg Air Force Base in California, the Air Force said.
The base did not give an exact time for the landing, but a notice to aviators and mariners on the Federal Aviation Administration's website said airspace around the Southern California base would be closed from 8 a.m. to 5 p.m. PT Tuesday.
"Team Vandenberg stands ready to implement safe landing operations for the X-37B Orbital Test Vehicle, the third time for this unique mission," Col. Keith Baits, commander of the 30th Space Wing, said in a statement.
The X-37B, which looks like a small space shuttle, lifted off from Cape Canaveral in Florida on December 11, 2012. At the time, the Air Force said its mission would last about nine months.
The X-37B "is designed to demonstrate reusable spacecraft technologies for America's future in space and operating experiments which can be returned to, and examined, on Earth," an Air Force statement said.
"Technologies being tested in the program include advanced guidance, navigation and control, thermal protection systems, avionics, high temperature structures and seals, conformal reusable insulation, lightweight electromechanical flight systems, and autonomous orbital flight, re-entry and landing."
But as the spacecraft has been in orbit for more than 22 months, speculation on other uses abounds, including testing of a secret space weapon or spying activities.
The previous mission of the X-37B, which landed at Vandenberg on June 16, 2012, lasted 469 days, according to the Air Force. That mission was flown by the second of the Air Force's two X-37B orbiters.
The current mission is the second for the first of the orbiters, which was refurbished after it spent 224 days in orbit following an April 2010 launch.
When the current mission launched, the Air Force said it might not be the last.
"Officials anticipate multiple missions will be required to satisfy the test program objectives, but the exact number of missions has not been determined," a statement said.
The X-37B spacecraft is 29 feet, 3 inches long and 9 feet, 6 inches high with a wingspan of 14 feet and 11 inches. It weighs about 5.5 tons. It is lifted into space by United Launch Alliance's Atlas V rockets.