LVMH said Abloh, 41, had been battling cancer privately for years.
"Virgil was not only a genius designer, a visionary, he was also a man with a beautiful soul and great wisdom," LVMH's billionaire boss Bernard Arnault said in a statement.
Abloh, a US national who also worked as a DJ and visual artist, had been men's artistic director for Louis Vuitton since March 2018.
In July this year, LVMH expanded his role, giving him a mandate to launch new brands and partner with existing ones in a variety of sectors beyond fashion.
A statement on Virgil Abloh's Instagram page said the family were devastated at the loss.
"For over two years, Virgil valiantly battled a rare, aggressive form of cancer, cardiac angiosarcoma," the statement read.
"He chose to endure his battle privately since his diagnosis in 2019, undergoing numerous challenging treatments, all while helming several significant institutions that span fashion, art, and culture.
"Through it all, his work ethic, infinite curiosity, and optimism never wavered."
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