He was born in Italy in 1931 and studied architecture in Milan and Venice from 1950 to 1957. After actively engaging in various projects, including designing posters and graphic materials for the 1964 Venice Biennale, he moved to the United States in 1956. In Chicago, he co-founded Unimark International, and in 1971, together with his wife and business partner Lella, established Vignelli Associates in New York.
From 1966 to 1980, he worked on the graphic program for Knoll; in 1966, he designed the New York subway sign system; in 1967, the American Airlines logo; in 1970, the New York subway map; and in 1995, the Benetton logo. He has been active across diverse design fields, including identity programs, posters, architecture, graphics, and products. From the earliest stages of his career until now, Vignelli has embodied modernism through organized and structured design.

He majored in visual design at Hongik University College of Fine Arts. He studied graphic design at Rhode Island School of Design and received a Ph.D. in art from Sungkyunkwan University. He worked as a graphic designer at Ssangyong Group Public Relations Office and Samsung Electronics Overseas Headquarters, and was a professor at Hanyang University College of Design, Samsung Design Institute (SADI), and Samsung Design Research Institute (IDS). As of 2016, he is a professor of Information Interaction Design at Yonsei University Graduate School of Communication and Yonsei University Underwood International College.