Ipatieff, a Muscovite by birth, became an officer in the Imperial Russian Army in 1887 and was educated at the Mikhail Artillery Academy (1889–92) in St. Petersburg. After further study in Germany and France he returned to the academy in 1898 and became professor of chemistry until 1906.

While in Munich (1897) Ipatieff achieved the synthesis of isoprene, the basic unit of the rubber molecule. On his return to Russia he carried out important work on high-pressure catalytic reactions. The first breakthrough in organic catalysis had been due to Paul Sabatier who had demonstrated the use of finely ground nickel to catalyze hydrogenation of unsaturated hydrocarbons (1897). Ipatieff greatly extended this work. He showed how it could be applied to liquids and demonstrated that the process became much more powerful and adaptable at high pressures. To this end he designed the so-called Ipatieff bomb – an autoclave that permitted the heating of substances under pressure to above their boiling point. Thus before World War I Ipatieff had synthesized isooctane, and had polymerized ethylene.

During World War I and after the revolutionary years in Russia Ipatieff held a number of important advisory posts, in addition to continuing with his own research, despite his anti-Communist feelings. In 1930, worried for his own safety, he traveled to America. Despite being 64 when he arrived in America Ipatieff still had much to offer, publishing over 150 papers in this last phase of his career. He was appointed professor of chemistry at Northwestern University, Illinois, (1931–35) and also acted as a consultant to the Universal Oil Products Company of Chicago who, in 1938, established at Northwestern University the Ipatieff High Pressure Laboratory, which he directed. With the growth of the petrochemical industry after 1918, Ipatieff's techniques became widely used. Working in America he showed how low-octane gasolines could be converted to high-octane gasoline by ‘cracking’ hydrocarbons at high temperatures.