Segrè was appointed assistant professor of physics at the University of Rome in 1932 and worked there until 1936, becoming one of the Via Panisperna boys. In 1934, he met Elfriede Spiro, a Jewish woman whose family had come from Ostrowo in West Prussia, but had fled to Breslau when that part of Prussia became part of Poland after World War I. After the Nazi Party came to power in Germany in 1933, she had emigrated to Italy, where she worked as a secretary and an interpreter. At first she did not speak Italian well, and Segrè and Spiro conversed in German, in which he was fluent. The two were married at the Great Synagogue of Rome on 2 February 1936. He agreed with the rabbi to spend the minimal amount on the wedding, giving the balance of what would be spent on a luxury wedding to Jewish refugees from Germany. The rabbi managed to give them many of the trappings of a luxury wedding anyway. The couple had three children: Claudio, born in 1937, Amelia Gertrude Allegra, born in 1937, and Fausta Irene, born in 1945.
After marrying, Segrè sought a stable job and became professor of physics and director of the Physics Institute at the University of Palermo. He found the equipment there primitive and the library bereft of modern physics literature, but his colleagues at Palermo included the mathematicians Michele Cipolla and Michele De Franchis, the mineralogist Carlo Perrier and the botanist . In 1936 he paid a visit to Ernest O. Lawrences Berkeley Radiation Laboratory, where he met Edwin McMillan, Donald Cooksey, Franz Kurie, Philip Abelson and Robert Oppenheimer. Segrè was intrigued by the radioactive scrap metal that had once been part of the laboratorys cyclotron. In Palermo, this was found to contain a number of radioactive isotopes. In February 1937, Lawrence sent him a molybdenum strip that was emitting anomalous forms of radioactivity. Segrè enlisted Perrier's help to subject the strip to careful chemical and theoretical analysis, and they were able to prove that some of the radiation was being produced by a previously unknown element. In 1947 they named it technetium, as it was the first artificially synthesized chemical element.