Born in Russia, Zetlin began his career in Israel and moved in 1950 to New York to earn his master's and doctorate from Cornell University.

After starting Lev Zetlin & Associates in 1956, he designed a number of structures that attracted the attention of architects such as Philip Johnson with whom he had a collaborative career.

Zetlin was later commissioned as a captain in the Israeli Air Force from 1948 to 1950[1] and fought in the 1948 Arab–Israeli War as a company commander in the Haganah,[2][4] overseeing the construction of transmission towers and other war-related structures.

Until 1948, he worked for Israel's Department of Agricultural and Industrial Settlements as chief structural engineer while maintaining his independent consulting practice which he continued to operate until 1950.

[1] He also briefly worked for the Ammann & Whitney firm in New York City where his first project was designing hangar structures at John F. Kennedy International Airport.

[12][13] By 1973, the firm was employing around 40 associates and was responsible for the structural design of airport terminals, bridges, high-rise apartments, hospitals, office buildings, offshore facilities, museums, schools and sports arenas.

[2][9] Zetlin later investigated the collapse of a walkway at the Hyatt Regency Hotel (Kansas City, Missouri) in 1981 that killed 113 people.

[17][18] Zetlin obtained a patent on this self-damping cable system and used it on other buildings such as the Salt Lake County Civic Auditorium.

[13] Among these was the Travelers Insurance Pavillion in which he used a set of boomerang-shaped frames and a tension belt of cables to create a structure in the form of an umbrella as in the company's logo.

[21] Zetlin was also the structural designer on the Kodak Pavillion for which he used a concrete shell of varying thickness to build the columns and cloud-like roof of the pavilion.

On top of this roof structure was a walkway that led visitors along sculptured fountains, pools of water, and a tower featuring Kodak photographs.

[22][23] Zetlin and Johnson worked together on several other projects[24] including the Niagara Falls Convention Center which used eight steel, space frame trusses to span the 365-foot (111 m) roof.

Zetlin used precast arch segments of wall and floor structures that can be assembled to create spaces in a variety of shapes.

[1] In 1964, the Concrete Industry Board honored Zetlin with a special award for the Eastman Kodak Pavilion at the New York World's Fair.

[1] In 1969, Zetlin was awarded the Gold Medal from the Société Arts, Sciences, Lettres in France largely because of his work on the 1964–65 New York World's Fair.

[1][25] He has twice won the Honor Award from the U.S. Department of Housing and Urban Development first for his work on the Bluebeard's Hill Apartments in Saint Thomas, U.S. Virgin Islands, in 1968, and the Charles Center in Baltimore, Maryland, in 1970.