The impressive line-up all performed from their homes in support of health workers after a six-hour pre-show broadcast got the audience excited.
The weekend's online party - backed by the international advocacy organisation Global Citizen in partnership with the World Health Organization - featured stars across the globe including Jennifer Hudson, Matthew McConaughey, Luis Fonsi and Kesha making appearances via video from their homes.
Singer Taylor Swift held back tears as she performed her song "Soon You'll Get Better", which she wrote about her mother's battle with cancer.
Former first ladies of the United States Michelle Obama and Laura Bush made an appearance, both thanking the frontline workers putting their health at risk to keep their communities running during the pandemic.
Soccer phenom David Beckham held a video chat with young athletes, encouraging them to keep honing their skills at home with sporting events canceled indefinitely.
Global Citizen intended for the event, which was not a fundraiser, to both entertain and act as a "rallying cry" to support health workers and action for charities on a local level, after raising $35 million to help fight the coronavirus.
Performers Christine and the Queens and Annie Lennox, actors Don Cheadle and Samuel L Jackson, and soccer star Megan Rapinoe also participated.
Adam Lambert performed a rendition of Tears for Fears' hit "Mad World," while The Killers delivered a stripped-back version of "Mr Brightside".
And Hudson belted out the Cats theme "Memory," with a pianist accompanying her elastic vocals.
"Let's remind ourselves here in these trying times there is still so much kindness, hope and joy in the world," Matthew McConaughey said.
Sarah Jessica Parker gave a shout out to medical workers toiling at the hard-hit hospital Elmhurst in New York, the US epicentre of the coronavirus pandemic.
"You are heroes," the Sex and the City star and New Yorker said from her couch.
"We are forever grateful for the sacrifices you have made to keep the community healthy and safe."
Before performing a soulful version of "Rainbow" in front of her fireplace, pop star Kesha also thanked health workers for "risking your life and your health and your sanity".
"I just think the vulnerability of us all as human beings right now is really showing a really beautiful side to humanity," she said, her cat meowing in the background.
In addition to celebrity appearances the streamed show highlighted the efforts of essential workers worldwide, including medical personnel and those delivering food and sanitary products to vulnerable populations.
Dressed in scrubs, hospital worker Aisha al Muntheri spoke from Paris to say she was proud to serve "on the front lines with my colleagues."
"It's part of our value in medicine to serve humanity," she said.
"The humanity is our common language."
'Love letter to the world'
The digital special preceded a Lady Gaga-curated virtual show that celebrated and supported the efforts of medical workers against coronavirus, which has at least 4.5 billion people forced or urged to stay home worldwide.
The two-hour primetime event was rife with A-listers including Billie Eilish, Elton John, Jennifer Lopez, Celine Dion, Paul McCartney and Stevie Wonder began at 10am AEST on Sunday morning.
American late-night television personalities Jimmy Fallon, Jimmy Kimmel, and Stephen Colbert shared the hosting duties, and all four Rolling Stones - Mick Jagger, Keith Richards, Charlie Watts and Ronnie Wood - gave a performance.
Lady Gaga told a WHO briefing ahead of the event it was intended to continue the "love letter to the world" that is the "fearless global effort" against COVID-19, which has left more than 157,000 dead worldwide.
The special "will continue this, telling global stories of triumph and hope, and told to a global audience, truly bringing the world together," Lady Gaga said.
"We can do something to bring joy and respite to the corners of the earth."
Global Citizen is urging philanthropists, companies and governments to support the WHO in its coronavirus response efforts, saying it has already raised $35 million for local organisations and the international health body's COVID-19 Solidarity Response Fund.
"Music provides this moment for us to pause to reflect to unite as one humanity," Global Citizen's CEO Hugh Evans said ahead of the event.
"And to come back together and say you know what, we truly - it's not just hyperbole - we truly are all in this together."
People in Australia must stay at least 1.5 metres away from others and gatherings are limited to two people unless you are with your family or household.
If you believe you may have contracted the virus, call your doctor (don’t visit) or contact the national Coronavirus Health Information Hotline on 1800 020 080. If you are struggling to breathe or experiencing a medical emergency, call 000.
SBS is committed to informing Australia’s diverse communities about the latest COVID-19 developments. News and information is available in 63 languages at sbs.com.au/coronavirus