Lopez studied high school at Colegio de San Juan de Letran, finishing in 1921. He studied law in the University of Santo Tomas, earning his Bachelor of Laws degree in 1925. After passing the bar examinations, he did not go into private practice, but helped his older brother manage the family business.
In 1945, with no prior political experience, Lopez was chosen by President Sergio Osmeña to be mayor of Iloilo City.[2] In 1947, he ran for senator and won.
The brothers Eugenio and Fernando owned the Iloilo-Negros Air Express Company (the first Filipino owned air service), the Iloilo Times (El Tiempo), the Manila Chronicle and ABS-CBN Corporation, LSC (Lopez Sugar Corporation), Bayantel (including Bayan DSL), SkyCable (including SkyBroadband), Meralco, RLC (Rockwell Land Corporation), Rockwell Center, First Balfour, Inc., Philippine Electric Corporation (Philec), First Electro Dynamics Corporation (Fedcor), First Sumiden Circuits, Inc. (FSCI), Securities Transfer Services, Inc. (STSI), The Medical City (TMC), BayanTrade DotCom, First Gas Holdings Corporation (Santa Rita), FGP. Corp. (San Lorenzo), FG Hydro Power Corporation (Pantabangan-Masiway), FG Bukidnon (Agusan mini-hydro), Bauang Private Power Corporation (Bauang), Panay Electric Company (PECO), First Philippine Industrial Corporation (the major fuel distributor of Shell and Chevron Caltex in the country), First Philippine Realty Corp, First Philippine Electric Corp. (First Philec), First Philec Solar Corporation, First Sumiden Circuits, Inc. (FSCI), First Sumiden Realty, Inc, First Philippine Industrial Park.
Vice-presidency
First term (1949–1953)
In 1949, Lopez became vice-president under President Elpidio Quirino and concurrently worked as secretary of agriculture, serving until 1953. He was then elected once again as senator, and re-elected in 1959.
Second and third term (1965–1972)
In 1965, Lopez ran with Ferdinand Marcos and won as vice-president. He was re-elected in 1969, making him, to date the only vice-president to serve two non-consecutive terms, two different presidents and from different parties. By the time martial law was declared in 1972, the Lopez family fell out of Marcos' favor and was targeted by the regime because of their denunciations of Marcos. The position of vice-president was abolished, and the Lopez family was stripped of most of its political and economic assets.
He died on May 26, 1993, a month after his 89th birthday leaving his wife Mariquit Javellana with whom he had six children: Yolanda, Fernando, Jr. (Junjie), Alberto (Albertito), Emmanuele, Benito and Mita. He was also the longest living vice president until he was surpassed by Teofisto Guingona Jr. in 2017.