Flight STS-106 was launched into a circular 350 km (189 nmi), 51.6° orbit to rendezvous for a servicing mission (2A.2b) with the International Space Station (ISS).

Atlantis carried 2,186 kg (4,817 lbm) of supplies and equipment to the space station, including 327 kg (722 lbm) of Russian hardware, 389 kg (858 lbm) of food, 356 kg (784 lbm) of fresh water generated by the shuttle and 522 kg (1,150 lbm) of exercise equipment. In addition the crew unloaded 588 kg (1,313 lbm) of supplies waiting in the Progress M1-3 cargo hold, including components for the Elektron oxygen generator, the carbon dioxide air scrubber and toilet components. Some of the Progress cargo was packed in U.S.-made bags that are easy to accommodate on the station and have specified preset locations. Other cargo, large components in boxes for the various systems, had to be installed into the locations where they would eventually be operated. Morukov was responsible for orchestrating the Progress unloading. Burbank directed stowage and assembly operations in the space station, while Mastracchio organized the unloading of the Spacehab module. One of the primary goals of STS-106 was to get Progress M1-3 off loaded to open that dock port for the next Progress flight, which was to deliver the remaining supplies required to support the first permanent space station crew, Expedition One.

Along with moving supplies into the station, this crew assembled a Russian Elektron oxygen generator, a carbon dioxide removal system and major components of the station's toilet. They also assembled a NASA-supplied treadmill and install laptop computers and equipment to set up a local area network. Two new batteries were installed in the Zarya module (four being previously replaced during the shuttle visit in May) and three batteries and their charge-discharge controllers were installed aboard Zvezda, giving the module a full complement of eight. To save on mass, Zvezda was launched with just five of its eight batteries installed and with many of its modular life support and control systems incomplete.

A spacewalk was conducted to connect power, data and communications cables between the Zvezda and Zarya, and to install a magnetometer.

Other objectives included:

• Installation of new software into computers in the Unity module to help control the P6 solar array upon its arrival
• Measurements of air quality in the station and the background acoustic environment
• Installation of air ducts and fans in Zvezda
• Removal of no-longer-needed manual docking control equipment in the Zarya module to make room for other equipment
• Installation of U.S.-to-Russian power converter units to enable Russian equipment to use power generated by the P6 solar array
• Installation of a bar code reader system to track station inventory and stowage locations
• Removal of launch restraint bolts from fire extinguishers in the Zvezda module
• Removal of Zarya's aft docking probe, which was no longer needed

Included on this Shuttle flight was an experiment that examined how microgravity alters gene expression in kidney cells, which enables kidneys to develop and function normally. This experiment increases the understanding of how the human body adapts to space, which ultimately may advance the knowledge of human disease processes.

Two tiny sensors tested by NASA on this flight made real-time measurements in the Shuttle's environmental and life support systems. Due to breakthroughs in miniaturization resulting in the introduction of a 1-inch in diameter wireless system the sensors can send temperature measurements to a laptop computer for five months. This new technology will reduce the time it takes to obtain on-orbit temperature measurements and increase the capability to monitor temperatures over long periods of time

Several student experiments were aboard, including one called "The Pittsburgh Steelers in Space," designed by students at the DePaul Institute for the Deaf in Pittsburgh, PA, to determine the effects of microgravity and radiation on the oxidation of various types of steel and the minerals involved in the manufacture of steel.

The mission performed two ISS reboosts with Atlantis and a shuttle flyaround of the ISS. The Atlantis used spare fuel remaining aboard the space shuttle to boost the space station's altitude by about six kilometers (three nautical miles), saving station propellant for use when the shuttle is not available.

The STS-106 crew was made up of Col. Terrence Wilcutt, Commander, 50, Scott Altman, Pilot, 41, and Mission Specialists Dr. Edward Lu, 37, Richard Mastracchio, 40, Daniel Burbank, 39, Col. Yuri Malenchenko, 38, and Dr. Boris Morukov, 49.