Virgil Abloh was born on 30 September 1980 in Rockford, Illinois, to Ghanaian immigrant parents; his mother was a seamstress who taught him to sew. He studied civil engineering at the University of Wisconsin–Madison, graduating in 2002, and then took a master's degree in architecture at the Illinois Institute of Technology, in the campus Mies van der Rohe had designed. Architecture shaped everything he did later. He liked to talk about design as a system, and about the "three per cent" rule, the idea that changing an existing object by a small amount was enough to make it new.

While still a student he was already working across music, graphics and clothing. He met Kanye West in the early 2000s, and in 2009 the two interned together at Fendi in Rome. Abloh became creative director of West's agency, Donda, overseeing album artwork, stage design and merchandise; the cover of Watch the Throne was nominated for a Grammy. In 2012 he launched a short-lived label, Pyrex Vision, which printed over deadstock Ralph Lauren flannel shirts.

The following year he founded Off-White in Milan. It treated streetwear with the seriousness of luxury, using quotation marks, industrial belts, diagonal stripes and zip ties as recurring signatures, and it was shown at Paris Fashion Week. In 2015 he was a finalist for the LVMH Prize. His 2017 collaboration with Nike, The Ten, reworked ten classic sneakers with exposed construction and handwritten labels, and it became one of the most sought-after releases of the decade. He also worked with Ikea, Evian, Rimowa and the Museum of Modern Art, and he was a working DJ throughout his career.

In March 2018 Louis Vuitton appointed him artistic director of menswear. He was the first African-American to hold the role at the house, and one of very few Black designers to lead a major French luxury brand. His first show, in June 2018 in the gardens of the Palais-Royal, used a rainbow runway and a cast that reflected his interest in diversity and youth. Over the following seasons his collections drew on tailoring, workwear, Black American cultural history and the idea of the tourist and the purist, and he made Louis Vuitton menswear a cultural event. In 2019 the Museum of Contemporary Art Chicago opened Figures of Speech, a retrospective of his work that later travelled to Atlanta and Boston. He was named one of Time's 100 most influential people in 2018.

He gave time to younger designers too. He lectured widely at universities, and in 2020 he set up the Post-Modern scholarship fund, with the Fashion Scholarship Fund, for students of Black, African-American or African descent. In July 2021 LVMH took a 60 per cent stake in Off-White and announced an expanded role for him across the group's brands.

That role did not last. Abloh had been diagnosed in 2019 with cardiac angiosarcoma, a rare cancer, and had kept his illness private while continuing to work. He died in Chicago on 28 November 2021, aged 41. Louis Vuitton went ahead with his final collection in Miami days later as a tribute, and his last menswear collection was shown in Paris in January 2022. He was survived by his wife, Shannon, and their two children.

His influence has outlived him. He showed that a designer could come from outside the fashion establishment and move between streetwear, art, architecture and luxury on equal terms, and that a large brand could be a platform for collaboration. Off-White continues under a new owner and new creative leadership, and Louis Vuitton's men's collections are now led by Pharrell Williams, another figure from music.