STS-135 (ISS assembly flight ULF7) was the 135th and final mission of the American Space Shuttle program. It used the orbiter Atlantis and hardware originally processed for the STS-335 contingency mission, which was not flown. STS-135 launched on July 8, 2011, and landed on July 21, 2011, following a one-day mission extension. The four-person crew was the smallest of any shuttle mission since STS-6 in April 1983. The mission's primary cargo was the Multi-Purpose Logistics Module (MPLM) Raffaello and a Lightweight Multi-Purpose Carrier (LMC), which were delivered to the International Space Station (ISS). The flight of Raffaello marked the only time that Atlantis carried an MPLM.

Although the mission was authorized, it initially had no appropriation in the NASA budget, raising questions about whether the mission would fly. On January 20, 2011, program managers changed STS-335 to STS-135 on the flight manifest. This allowed for training and other mission specific preparations. On February 13, 2011, program managers told their workforce that STS-135 would fly regardless of the funding situation via a continuing resolution. Until this point, there had been no official references to the STS-135 mission in NASA documentation for the general public.

During an address at the Marshall Space Flight Center on November 16, 2010, NASA administrator Charles Bolden said that the agency needed to fly STS-135 to the station in 2011 due to possible delays in the development of commercial rockets and spacecraft designed to transport cargo to the ISS. "We are hoping to fly a third shuttle mission (in addition to STS-133 and STS-134) in June 2011, what everybody calls the launch-on-need mission... and that's really needed to [buy down] the risk for the development time for commercial cargo", Bolden said.

The mission was included in NASA's 2011 authorization, which was signed into law on October 11, 2010, but funding remained dependent on a subsequent appropriations bill. United Space Alliance signed a contract extension for the mission, along with STS-134; the contract contained six one-month options with NASA in order to support continuing operations.

The federal budget approved in April 2011 called for US$5.5 billion for NASA's space operations division, including the shuttle and space station programs. According to NASA, the budget running through September 30, 2011, ended all concerns about funding the STS-135 mission.

NASA announced the STS-335/135 crew on September 14, 2010. Only four astronauts were assigned to this mission, versus the normal six or seven, because there were no other shuttles available for a rescue following the retirement of Discovery and Endeavour. If the shuttle was seriously damaged in orbit, the crew would have moved into the International Space Station and returned in Russian Soyuz capsules, one at a time, over the course of a year. All STS-135 crew members were custom-fitted for a Russian Sokol space suit and molded Soyuz seat liner for this possibility. The reduced crew size also allowed the mission to maximize the payload carried to the ISS. It was the only time that a Shuttle crew of four flew to the ISS. The last shuttle mission to fly with just four crew members occurred 28 years earlier: STS-6 on April 4, 1983, aboard Space Shuttle Challenger.

With support from both the House of Representatives and the Senate, the fate of STS-135 ultimately depended on whether lawmakers could agree to fund converting the mission from launch-on-need to an actual flight. On July 15, 2010, a Senate committee passed the 2010 NASA reauthorization bill, authored by Senator Bill Nelson (D-FL), to direct NASA to fly an extra Space Shuttle mission (STS-135) pending a review of safety concerns. The bill still needed the approval of the full Senate. A draft NASA reauthorization bill considered by the House Science & Technology Committee did not provide for an extra shuttle mission. On July 22, 2010, during a meeting of the House Science Committee, U.S. Rep. Suzanne Kosmas (D-FL) successfully amended the House version of the bill to add an additional shuttle mission to the manifest.

On August 5, 2010, the Senate passed its version of the NASA reauthorization bill, just before lawmakers left for the traditional August recess. On August 20, 2010, NASA managers approved STS-135 mission planning targeting a June 28, 2011, launch. On September 29, 2010, the House of Representatives approved the Senate-passed bill on a 304–118 vote. The bill, approved by the U.S. Congress, went to President Barack Obama for his signature.