On October 12, 2000, the Discovery Shuttle (STS-92) was launched (ISS program, flight 3A) which docked to the ISS on October 13. Using the remote manipulator, a section of the base truss Z1 was mounted on the Unity module, the ISS was equipped with a pressurized adapter, Ku-band radio system and gyrodynes; four EVAs were performed. The ISS is prepared to receive the first prime crew (ISS-1). The complex consisting of Progress M1-3 cargo vehicle - Zvezda service module - Zarya functional-cargo module - Unity module - Discovery orbiter was formed in orbit. The Discovery orbiter performed landing on October 24, 2000.

On October 31, 2000, the Soyuz TM-31 transport vehicle with the ISS first prime expedition crew on board was launched. The crew consisted of two Russian cosmonauts - Yu. Gidzenko and S. Krikalev - and American astronaut W. Shepherd. The launch was performed by the Soyuz-U launch vehicle from the Baikonur cosmodrome. On November 2 the Soyuz TM-31 TV docked successfully with the ISS. With arrival of the first prime expedition crew to the ISS the station has become permanently inhabited. The complex consisting of Soyuz TM-31 - Zvezda - Zarya - Unity with a mass of about 73 t was formed in orbit.

On November 16, 2000, the Progress M1-4 transport cargo vehicle was launched from the Baikonur cosmodrome; on November 18 it was docked to the side port of the Zarya module. The cargo vehicle delivered 2.2 t payload to the ISS: propellant, food, water, medical supplies, flight equipment including units and devices of the station's systems. The complex consisting of Unity - Zarya - Zvezda - Soyuz TM-31 - Progress M1-4 with a mass of about 80 t was formed in orbit. On December 1 the Progress M1-4 TCV was undocked from the ISS on-orbit complex. On the 1st of December 4 Progress M1 undocked from the International Space Station, and on the 26th of December it redocked to the ISS. On the 8th of February Progress M1-4 undocked from the ISS and was de-orbited along the descent trajectory to the oceanic area.

On December 1, 2000, the Endeavour Shuttle STS-97 (ISS program, flight 4A) started; on December 2 it was docked to the docking assembly of the U.S. Unity module. At the moment of the orbiter docking to the ISS complex the Progress M1-4 vehicle was in autonomous flight. Through December 8 the Endeavour crew implemented the program of work planned within the STS-97 flight: delivered to the complex and mounted the truss with two panels of solar arrays to improve the station power supply before arrival of the U.S. Destiny laboratory to the station. On December 8, after opening of the transfer hatch to the Russian Zvezda service module the meeting of two crews - the ISS on-orbit complex crew and the Endeavour orbiter crew - took place; then joint activities began on transfer of delivered cargoes to the ISS. The on-orbit complex of about 187 t in mass functioned in the configuration: Soyuz TM-31 - Zvezda - Zarya - Unity - Endeavour. On December 12, 2000 The Endeavour Shuttle performed successful landing.

On February 8, 2001 the Space Shuttle Atlantis STS-98 (ISS program, flight 5A) was launched. On February 9 it docked to the ISS. The crew consisted of NASA astronauts, i.e. Kenneth Cockrell (commander), Mark Polansky (pilot), Robert Curbeam, Marsha Ivens and Thomas Jones (mission specialists). The Atlantis crew delivered and docked the Laboratory module Destiny, as well as delivered water, air food supplies and equipment for the Expedition I crew (ISS-1) to the station.
On February 16 the Atlantis crew performed undocking, and on February 20 successfully landed.
The complex consisting of the Souyz TM-31 manned vehicle, Russian Service Module Zvezda, Functional Cargo Block Zarya, U.S. modules Unity and Destiny was formed in orbit. The Station mass was about 105 t.