The One World: Together At Home show will see more than 100 artists including the Rolling Stones and Billie Eilish play live from their homes.
Lady Gaga, who helped organise the concert, will also perform.
The eight-hour event run by the Global Citizen movement and the World Health Organization (WHO) is being live-streamed and broadcast on TV.
"We may be apart right now, but coming together has never been more important," Global Citizen said in a statement.
The event will also be telling real-life stories of nurses and doctors fighting the coronavirus outbreak.
Proceeds generated from the concert will go to the Covid-19 Solidarity Response Fund for WHO.
But Lady Gaga has made clear that the show is not a fundraising telethon and will focus on entertainment and messages of solidarity.
American TV personalities Stephen Colbert, Jimmy Kimmel and Jimmy Fallon will host the show, which will also feature Taylor Swift, Jennifer Lopez, Chris Martin, Pharrell Williams, Rita Ora, Sam Smith, Elton John and Paul McCartney.
The show starts with a six-hour pre-concert at 19:00 BST on Saturday, followed by the main two-hour TV broadcast at 01:00 BST on Sunday.
The entire event will be streamed live on Amazon Prime Video, Facebook, Instagram, TuneIn, Twitch, Twitter and YouTube; with Apple, Music, Apple TV, and Apple Beats 1 joining for the main show.
In the UK, BBC One will screen highlights of the concert at 19:15-21:15 BST on Sunday.
It will include extra performances from British artists like Little Mix, Sir Tom Jones and Rag 'N' Bone Man and additional footage will also be available on BBC iPlayer for 30 days.
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