Cardi B, who opened the night by introducing a Shawn Mendes performance, was another big victor, taking home trophies for the Lopez collaboration, best new artist and song of the summer for "I Like It", which she'd recorded alongside Bad Bunny and J Balvin.
She said: "Welcome to NY everybody, I am the empress, the liberals voted for me".
As she accepted her Best New Artist accolade, she proudly proclaimed she had defied her critics. "A couple of months ago, a lot of people were saying, 'You're gambling your career, you're about to have a baby, what are you doing?' And you know, I had a baby, I carried the baby, and now I'm still winning an award!" Beyonce, Jay-Z, Rihanna and Kendrick Lamar were restricted to technical honors like editing, art direction, cinematography and visual effects.
Canadian rapper Drake, one of the most popular artists in terms of sales and streaming, came away empty-handed, as did multiple Grammy victor Bruno Mars.
Ariana Grande performs onstage during the 2018 MTV Video Music Awards at Radio City Music Hall on August 20, 2018 in New York City.
Madonna Gives Aretha Franklin a Baffling Tribute at the 2018 VMAs
This is a jovial kiki about Madonna's broken a- journey. "Love you Madonna , but what was supposed to be a tribute to the "Queen of Soul", you made it all about you".
The New York native's comments came just before she was presented with the Michael Jackson Video Vanguard Award - she also has two nominations for her flashy new "Dinero" video.
The 21-year-old won video of the year and artist of the year.
"The pop icon rambled and rambled about the early struggles in her career, finally informing the crowd that she sang Franklin's "(You Make Me Feel Like) A Natural Woman" at an audition that became a breakthrough for her.
The VMAs have a reputation for irreverence and provocative stunts but, aside from a segment on US President Donald Trump's controversial immigration policies, there were few surprises.
The song is a protest against the policy that saw thousands of immigrant children separated from their parents in June after crossing the southern border with Mexico without documents.