Launch from Cape Canaveral (KSC); landing at Cape Canaveral (KSC); ISS-1J/A JEM ELM PS / SLP-D1.

STS-123 delivered the first module of the Japanese laboratory, Japanese Experiment Module (Kibo), and the Canadian Special Purpose Dexterous Manipulator, (SPDM) Dextre robotics system to the station. The mission duration was 16 days and 14 hours, and it was the first mission to fully utilize the Station-to-Shuttle Power Transfer System (SSPTS), allowing space station power to augment the shuttle power systems. The mission set a record for a shuttle's longest stay at the ISS.

Following a two day solo flight Endeavour docked to the ISS on March 13, 2008. Common work with the ISS expedition 16 was performed. Garrett Reisman was tranferred to the ISS and Léopold Eyharts to the STS-123 crew for returning to the Earth.

The first EVA by Richard Linnehan and Garrett Reisman occured on March 14, 2008 (7h 01m) to prepare the JEM ELM PS for its removal from the shuttle's payload bay. Later that day, the Japanese facility was installed on top of the Harmony module.

The second EVA by Richard Linnehan and Michael Foreman was performed on March 16, 2008 (7h 08m) to assemble Special Purpose Dexterous Manipulator (SPDM), named Dextre by removing covers and installing arm components on its main body.

The third EVA was conducted by Richard Linnehan and Robert Behnken on March 17, 2008 (6h 53m) to complete Dextre assembly by installing a tool platform and tool holster assembly.

The fourth EVA by Robert Behnken and Michael Foreman occured on March 20, 2008 (6h 24m) to evaluate the Shuttle Tile Ablator-54, or STA-54, material and a tile repair ablator dispenser for use as a shuttle thermal protection system repair technique. The Tile Repair Ablator Dispenser, or T-RAD, is similar to a caulk gun. They used TRAD to mix and squirt out the STA-54 material into holes in several demonstration tiles. The repaired samples will be returned to Earth for extensive testing.

The fifth and final EVA was performed by Robert Behnken and Michael Foreman on March 22, 2008 (6h 02m) to move the Orbiter Boom Sensor System, the 50 ft. extension of the shuttle's robotic arm, to a temporary location on the station's main truss or backbone. The OBSS was left on the station because shuttle Discovery doesn't have enough room in its cargo bay to carry both the boom and the large Japanese pressurized module on the STS-124 mission. The spacewalkers also installed a new trundle bearing assembly in the starboard Solar Alpha Rotary Joint to allow the joint to rotate a little bit more if necessary. That SARJ has had limited ability for several months, and metallic debris has been found inside it. Additional spacewalk tasks included inspecting the SARJ and collecting debris samples.

Flight controllers gave a no-go on de-orbit for the first landing opportunity at 23:05 UTC (19:05 EDT), due to unfavorable weather conditions at the Shuttle Landing Facility at Kennedy Space Center. Weather conditions were acceptable for the second landing opportunity, planned for 00:39 UTC March 27, 2008 (20:39 EDT March 26, 2008). The landing occurred at the Shuttle Landing Facility, and was the sixteenth night landing of the Space Shuttle at KSC, 22nd Shuttle night landing overall. Coincidentally, this mission also began with a night launch.

Garrett Reisman landed on June 14, 2008 at 15:15 UTC with STS-124.