It has the following improvements:[2][3][4][5] A Soyuz-2.1a launched Progress MS-16 to the International Space Station from Baikonur Cosmodrome Site 31 on 15 February 2021 following a two-day, 34-orbit rendezvous profile.

[1][6][7] Progress MS-16 was docked on 17 February 2021, 06:26:47 UTC, using manual docking system operated by Expedition 64 commander Sergey Ryzhikov to the Pirs module of the ISS, where it remained until 26 July 2021, 10:55 UTC.

[8] On 4 February 2021, Roscosmos said that Progress MS-16 had been installed back into its processing stand inside the assembly building at Site 254 for final pre-launch operations and loading of fresh food items in its cargo bay.

[1] The Progress MS-16 was expected to remain docked at the station until 23 July 2021, 12:45 UTC, when it would depart with the Pirs module docked to it for destructive reentry four hours later over the South Pacific Ocean, which would also mark the first module to be decommissioned from use aboard the International Space Station.

However, due to post-launch telemetry and propulsion issues with Nauka, the undocking of Progress MS-16 was delayed to 26 July 2021, at 10:55 UTC.