Ramón was born in Cartagena to an engineer working on the Valencian port of Castellón. He was a brother-in-law (cuñado) of Francisco Franco. Along he was an excellent student, his father disapproved of his aspirations to become a lawyer. He matriculated at Madrid University studying law anyway, and while he was there, studied along with Jose Antonio Primo de Rivera (who was later to become a Spanish dictator). He also spent a year in Bologna, during which he developed a taste for fascism.
Not only was Ramón Serrano Suñer brothers-in-law with Francisco Franco, the two also married a pair of sisters: Suñer married Zita Polo y Martinez-Valdès, whom he had met shortly after moving to Zaragoza, in 1931, while Franco married Carmen Polo y Martinez-Valdès. Ramón Serrano Suñer and Zita Polo had six children.
Although he had originally refused to become a member of the Falange, Suñer joined Franco early in the Spanish civil war (1936–39), as a conservative member of the Cortes (1933–36), during which he led the Falange. In July 1936 he was caught participating in the conspiracy to overthrow the republic and captured and locked in a Republican prison. He escaped, however, in October 1936, dressed as a woman. He was then aided by the Argentine navy in getting to France, from where he could reach Salamanca, where Franco was in office at the time. It was there that he could work with Franco to participate in the rebellious side of the Spanish Civil War. Escaping from prison amidst the cross-fire of an angry outbreak of his country's civil war, while both of his brothers were killed by the Republicans, it seemed ironic at the time that Suñer would not only manage to pull through but later live to be a centenarian.
He served as Nationalist minister of the interior (1937–40), and minister of the press and propaganda (1939–40), when he founded EFE. He was also appointed minister of foreign affairs (1940–42), thanks to his skill at building a relationshp with Benito Mussolini.
Even though he was working alongside Franco, he objected to the increasing role of the Roman Catholic church in Falangist politics. The two brothers-in-law had some intra-party conflicts of their own, as Suñer accused Franco of riding on a "cult of personality", while Franco viewed Suñer as increasingly becoming a thorn in the side of his party, criticizing too many of its policies.
In 1940, Suñer, Franco and Adolf Hitler met in southern France to discuss having Spain participate in World War II as part of the Axis. After playing a major role in establishing the Spanish state under Franco -- he was so influential as to be nicknamed the "Cuñadísimo" -- despite Serrano Súñer's advocating for Spain to join the Axis powers, Franco opted for Spain to remain a nonbelligerent during World War II. Hitler was disappointed that Suñer had not tried harder to help Germany, and called him the "gravedigger of the new Spain".
In 1942, Serrano Súñer was forced to resign as foreign minister and president of the political council of the Falange. After World War II, he wrote a persuasive letter to Franco, calling for a transitional government that would have room for intellectuals in exile. When Franco received the letter, he wrote a derisive "Ho-ho." in its margin. Súñer ultimately retired from public life in 1947.