Natta, who was born at Imperia in Italy, was educated at the Milan Polytechnic Institute where he obtained his doctorate in chemical engineering in 1924. He was professor at the University of Pavia (1933–35), the University of Rome (1935–37), and the University of Turin (1937–38). Natta returned to Milan in 1939 as professor of industrial chemistry. In 1963 he became the first Italian to be awarded the Nobel Prize for chemistry, which he shared with Karl Ziegler for their development of Ziegler–Natta catalysts.

Natta's early work was on x-ray crystallography and on catalysis. In 1938 he began to organize research in Italy for the production of synthetic rubbers – work that led him on to his discoveries in polymer chemistry. Ziegler in 1953 had introduced catalysts for polymerizing ethene (ethylene) to polyethene (polythene) – these catalysts gave straight-chain polymers producing a superior form of polyethene. Natta applied these catalysts (and later improved catalysts) to propene (CH₃CHCH₂) to form polypropene. In 1954 he showed that polymers could be formed with regular structures with respect to the arrangement of the side groups (CH₃–) along the chain. These so-called stereospecific polymers had useful physical properties (strength, heat resistance, etc.). Natta extended the technique to the polymerization of other molecules.