His series of powerful and enduring furniture design with Knoll Associates in the 1950s, though brief, provided him with enough royalties, allowing him to turn focus on sculpture for the rest of his life. It wasn't until 1930 until the 1915, Italian-born Bertoia moved with his moved with his parents to America , where he attended Cass Technical High School in Detroit . In 1937, he went to the Cranbrook Academy of Art on a scholarship. His professional life started in no time, though he first concentrated on printmaking and drawing, and sold his work through a gallery in New York . From 1939 until 1943, after establishing a metalworking and jewelry studio there, he became head of the department, and remained in the position for four years.

It was at Cranbrook where Bertoia's relationship colleagues Charles and Ray Eames extended into a complex working relationship. After marrying Brigitta Valentines, Bertoia joined the Eames in their California studio in 1943 where at that time they were working on wartime projects for the Evans Product Company by providing technical work for airplane and medical equipment. As Bertoia worked on drawing training manuals, they also started to experiment with molded plywood under the auspices of their Plyformed Products Company. Eventually, together with Eero Saarinen they developed a method for making molded plywood splints, a method that would later evolve into processes for designing furniture. Though the company was later bought out by Evans, Bertoia continued to work on a variety of projects and remained as part of their staff until 1946, leaving only because, conjecture reports, he felt unduly overshadowed by the Eames and was not receiving any specific credit for his work, a recurring complaint from the busy office during that period.

In the 1950's, Florence Knoll, another Cranbrook classmate who had a studio in Pennsylvania offered Bertoia a flexible and supportive environment in which to design. It was there that his immensely popular and controversial steel mesh series of furniture was produced, including one of the most prevalent images of modern furniture design, the "Diamond" chair. A piece grown out of a sculptural aesthetic, Bertoia himself described it to be a chair where "space passes through them." With such delicate and skeletal frames, the chairs were produced with varying degrees of upholstery over their light gridwork, and had to be handmade since no suitable mass production process could be found. What made the work controversial was the legal dispute the chair caused between two companies. Apparently, the chair so-closely resembled an Eames chair that Herman Miller, Eames' distributor, took Knoll to court on the grounds that they were taking wrongful credit for a bent-wire technique owned by the Eames. Though Herman Miller eventually won and ended up giving Knoll a license to produce the chairs, the fact that Eames and Bertoia worked closely for so long, the "genealogy" of inspiration seems difficult and maybe even unnecessary to pin down.

Bertoia retired from furniture design after the 1950s. Not that it kept him from working. The next twenty years saw Bertoia as a consultant to Knoll. By exploring the ways in which metal could be manipulated to produce sound, Bertoia, with his own sculptural work, continued to push furniture design to its limits by making it respond to wind or to touch to create various tones which he did by stretching and bending the metal. Out of this he created music made by his art which he performed with in a number of concerts. As if that wasn't enough, he even produced an album which he called Sonambient.