Although Hernández lacked books and money, with the help of the local vicar he became familiar with classical authors such as Miguel de Cervantes as well as more modern authors inlcuding Juan Ramón Jiménez, Rubén Darío, and Paul Valéry. In 1931, Hernández left for Madrid to try and establish a literary career. After a few months, he was forced to return home for lack of money-one many such excursions that would take place over the course of the next two years.
Back in Orihuela, Hernández became very interested in the works of Góngora, a hermetic poet from the 1600s, as well Góngora's contemporary imitators such as Rafael Alberti. The difficult metaphors and classical forms favored by these writers exerted a strong influence on Hernández's first book, Perito en lunas (Lunar Expert), which was published in 1933. In 1934, he published his first play, Quién te ha visto y quién te ve y sombra de lo que eras (He Who Has Seen You and He Who Sees You and the Shadow of What You Were).
No longer unknown, he returned to Madrid in 1934 where he became friends with writers such as García Lorca, Pablo Neruda, Luis Cernuda, and many others. His career as a writer developed rapidly. He worked with Neruda on the publication of the influential journal, Caballo Verde para la Poesía, and became involved with a group of writers supporting the Republican cause. In 1936 he published El rayo que no cesa (Unceasing Lightning). In 1937, he married his boyhood sweetheart, Josefina Manresa. They had a son, Manuel Ramón, in 1937, but he died in less than one year. Hernández's poems from this time moved away from the baroque style of his early work and employed a much more direct, surprising, and sensual language.
During the Spanish Civil War, Hernández served in the Republican Army. He depicted the horror of the war in much of his subsequent work, including Viento del pueblo (1937) and El Hombre acecha (1938). In 1939 while trying to flee to Portugal, he was arrested by the Guardia Civil and imprisoned in Madrid. While in prison, he continued to write. After his influential friends secured his release, Hernández returned briefly to Oriheuela before again being arrested. While in prison, he contracted tuberculosis. For the next three years, Hernandez wrote what many consider to be his most important poems. He died on March 28, 1942, while still in prison. On the wall next to his cot, he wrote his final poem: "Farewell, brothers, comrades, friends: Give my goodbyes to the sun and the wheat fields."