Between 1938 and 1940, Meltzer worked in the general counsel's office of the Securities and Exchange Commission and later as special assistant to chairman Jerome Frank, a fellow Chicago alumnus.

He also helped to draft the initial Lend-Lease agreements with allied nations and attempted, without success, to gain government approval for funding to liberate Jews in Eastern Europe who were being threatened with deportation and extermination by Nazi forces.

On December 8, 1941, the day after the Attack on Pearl Harbor, Meltzer tried to enlist in the Navy but was ultimately rejected due to his poor eyesight.

[3] In 1946, Meltzer was recruited by Francis M. Shea, a New Dealer and member of the Franklin D. Roosevelt administration, to serve as a prosecutor at the Nuremberg Trials.

[2][3] Meltzer carried out the pre-trial interrogation of Hermann Goering, Hitler's second-in-command, and presented the prosecution case at trial against Walther Funk, who was the Economics Minister and President of the Reichsbank during the war.

While at the law school, he developed ties with distinguished legal scholars Harry Kalven and Hans Zeisel, both of whom assisted Meltzer with the establishment of the law school's Jury Project to integrate the techniques and methodologies of the social sciences into legal research,[3][4] and Nobel laureates Milton Friedman, George Stigler and Ronald Coase.

He was survived by his wife, Jean Sulzberger, his daughters Joan FitzGibbon and Susan Yost and son Daniel Meltzer, and six grandchildren.