The song debuted at number one on the Billboard Hot 100 this week. This marks Grande's fourth song to debut at number one and Gaga's fifth overall.
Fans have been supporting the song since its May 22 release and made history in multiple ways, according to Billboard.
This new song makes the 26-year-old singer the first artist to record four songs that debuted in the top spot.
She most recently earned the top spot with her Justin Bieber collaboration, Stuck With U, on May 23.
Her hit songs Thank U Next and 7 Rings, both off of her 2019 album Thank U Next, both also debuted at number one.
The previous record for most number one debuts was three, held by Drake, Mariah Carey and Bieber.
Gaga (born Stefani Germanotta) becomes the third solo artist to earn number ones in three decade, the 00s, 10s, and 20s, alongside Carey and Beyonce.
For the Poker Face singer, Rain on Me also gave her a new record span of number one debuts, going nine years, three months and one week between debuts.
Her last debut at the top spot was 2011's Born This Way.
The dance-pop song also replaced Megan Thee Stallion and Beyonce's number one, Savage Remix, marking the first time a song by two women also replaced a song with multiple female artists.
Rain On Me it tracked over 72,000 digital downloads, the most of the week and more than 31m streams, earning the second most streaming totals for the week.
The new track is Gaga's official second single from her upcoming album, following on from her first song Stupid Love and the star says it is 'a metaphor for tears'.
Speaking to Zane Lowe on his Beats 1 radio show, she explained: '['Rain ON Me'] is also a metaphor for tears and for the amount of alcohol I was taking to numb myself.
'I'd rather be dry but at least I'm alive, rain on me.' And Gaga, 34, said she and Grande - who has battled with a number of tragedies in her life in the past few years, including the bombing at her 2017 Manchester Arena gig and the death of her ex Mac Miller - bonded while working on the song.
Gaga explained: 'That woman has been through some really tough, really hard life testing stuff, undoubtedly. And her ability to move on...'
'To be with her and hold her and be like, "Anything that you feel chains you, any pop cultural construct that you feel you have to live up to, I'd like you to please forget about it and be yourself."
© Associated Newspapers Ltd.