By 1964, Mangold had moved into his signature Minimalist painting style and had his first solo exhibition, Walls and Areas, at Fischbach Gallery in New York City. He subsequently participated in several seminal group exhibitions, including Systematic Painting held at the Solomon R. Guggenheim Museum in 1966, and Primary Structures, at the Jewish Museum in 1967. Mangold held various teaching positions, among them the School of Visual Arts in New York, Hunter College, Skowhegan School of Painting and Sculpture, Yale Summer School of Music and Art, and Cornell University Summer Art School. After receiving a Guggenheim Memorial Fellowship in 1969, Mangold and his wife, Sylvia Plimack Mangold, moved to upstate New York where they still live and work.
Major museum exhibitions of his work have been held at the Solomon R. Guggenheim Museum in New York (1971); the Museum of Contemporary Art in San Diego (1974); the Stedelijk Museum in Amsterdam (1982); Hallen für Neue Kunst in Schaffhausen (1993); the Musée D’Orsay in Paris (2006); the Albright Knox Art Gallery (2009), Buffalo, New York; Parasol Unit (2009), London; and the Kemper Museum of Art (2016-17), Kansas City, Missouri. His work has been featured in the Whitney Biennial four times in 1979, 1983, 1985, and 2004 and is included in approximately 100 international public collections.