#NoTearsLeftToCry also trended worldwide on Twitter.
The new music comes just over a month before the anniversary of the Manchester Arena attack on 22 May.
The video for No Tears Left To Cry features a bee flying off screen at the end, a symbol of solidarity with Manchester.
The worker bee has appeared on Manchester's coat of arms since the 1800s as an emblem of the city's hard-working past.
Grande's concert was targeted by suicide bomber Salman Abedi, who detonated a homemade device in the venue's foyer.
Twenty-two people were killed and more than 500 injured in the deadliest UK terror attack since the 2005 London bombings.
The pop star said she was left "broken" by the attack.
Ariana Grande left cryptic messages on Instagram and Twitter hinting at a new song.
The 24-year-old has been teasing new music on social media since Tuesday.
She posted a teardrop emoji on Twitter, telling fans "missed you", along with cryptic messages alluding to new music.
Her 30-second teaser clip of the video was watched on Twitter more than a million times.
The pop star had not posted on social media since January.
She had been reluctant to return to the studio after the attack, but now sings in her new track: "Right now I'm in a state of mind I want to be in, like, all the time."
Grande became Manchester's first honorary citizen after her response to the bombing.
She organised the One Love Manchester concert just two weeks later, persuading stars including Katy Perry, Justin Bieber, Coldplay and Liam Gallagher to perform in tribute.