Donning an impressive three outfits on the night, the 40-year-old singer not only opened the ceremony with a stunning medley of hits, but also walked away with the gala's top award, the Legend for Outstanding Contribution to the Arts.
The Latina star began the evening by walking the red carpet with husband Marc Anthony in a leopard-print Roberto Cavalli gown.
Then she slipped into a sparkly silver mini-dress with a fringed skirt for her performance.
Finally, it was into another animal-inspired Cavalli creation – a tiger-print evening gown – to accept her prestigious prize, previous recipients of which have included Michael Jackson, Sir Elton John and Madonna.
The Love Don't Cost a Thing singer said she was honoured to receive the award but hoped she was "just at the beginning" of a long musical career.
Jennifer is currently cruising the Mediterranean with Marc and their baby twins Max and Emme on designer Roberto Cavalli's luxury yacht.
The star, who hopes to release her seventh studio album later this year, has been busy partying in Cannes, taking in the Monaco Grand Prix and out shopping in Saint-Tropez in recent days.
Other winners on the night included Lady Gaga, who picked up four awards – best single, best album, best new artist and best pop/rock artist – though was unable to attend in person.
The Black Eyed Peas also did well, with will.i.am collecting best pop artist, best R&B artist and best hip hop artist for the foursome.
Hosted by Avatar's Michelle Rodriguez and Heroes actress Hayden Panettiere, the ceremony also proved something of a family get-together for the Hilton clan.
Socialite siblings Paris and Nicky attended alongside their 20-year-old brother Barron and parents Kathy and Rick.
Other notable guests at the prize-giving included singers Peter Andre, Kelly Rowland and Andrea Bocelli, as well as model Karolina Kurkova.