Growing up in Warsaw, Zames and his family escaped the city at the onset of World War II, and moved to Kobe (Japan), through Lithuania and Siberia, and finally to the Anglo-French International Settlement in Shanghai.

In 1965, Zames received a Guggenheim Fellowship and moved to the NASA Electronic Research Center (ERC), where he founded the Office of Control Theory and Applications (OCTA).

In 1972, Zames spent a sabbatical at the Technion in Haifa, Israel, and in 1974, he returned to McGill University to become a professor and eventually the MacDonald Chair of Electrical Engineering until his death in 1997.

Zames’s research focused on imprecisely modelled systems using the input-output method, an approach that is distinct from the state space representation that dominated control theory for several decades.

At the core of much of his work is the objective of complexity reduction through organization:[4] For the purposes of control design, gross qualitative properties such as robustness can be analyzed and predicted without depending on accurate models or syntheses.