After World War II Ramo joined Hughes Aircraft Company to launch an entirely new approach to defense electronics. He hired the most talented scientists and engineers and motivated them to apply the latest discoveries to radar and missiles. In a few years Hughes (now known as Raytheon Electronics) became one of the largest and most successful hi-tech companies in the world. Ramo was the Vice President for Operations over R&D, Product Engineering, and Manufacturing. He recruited, formed and led the Hughes teams that never lost a contract competition during that era. When he left Hughes in 1953, it was the largest concentration of technical talent that specialized in military electronics and guided missiles in one location in the country. Developments at Hughes were basic to the air superiority of the U.S. and were an extremely important contribution to national security since every interceptor airplane built in the U.S., to prevent enemy planes from successful bombing of the nation, was equipped with radar, computers, navigation systems and guided missiles developed and manufactured by Hughes.

A major factor in the Hughes success was its development of "systems engineering," the design of the "whole" (the solving of complex interdisciplinary problems and the ensuring of a harmonious, optimum ensemble of hardware and information flow to reach desired overall systems performance). On this and other pertinent engineering innovations, Ramo wrote many articles, authored and co-authored a number of texts and delivered numerous invited lectures at universities and National Academy and professional society meetings. (When Ramo left Hughes in 1953, he persuaded Howard Hughes to donate the company to the Howard Hughes Medical Foundation. Later, after Howard Hughes died, the company was sold by the Foundation to General Motors for around $5 billion.)