Born in Goddelau near Darmstadt, Germany, as the son of a doctor, Büchner frequented a Humanist secondary school that focused on languages, including modern languages (French, Italian and English). Nevertheless Büchner studied medicine in Strassburg.
In 1828 he became interested in politics and joined a circle of Shakespeare aficionados which later on probably became the Giessen and Darmstadt section of the "Gesellschaft für Menschenrechte". In Strassburg, he got to know both French literature and political thought. In 1835, Büchner translated two works by Victor Hugo, Lucrèce Borgia and Marie Tudor. Two years later, his dissertation, "Mémoire sur le système nerveux du Barbeaux (Cyprinus barbus L.)" was published in Paris and Strassburg. He was influenced by the utopian communist theories of Babeuf and Saint-Simon.
While he continued his studies in Giessen he established a secret society dedicated to the revolutionary cause. He printed leaflets called Der Hessische Landbote\, aimed at the political education (or indoctrination, depending on point of view) of peasants. However, due to treason Büchner had to leave the country and fled to France.
In 1835, his first play, Dantons Tod, about the French revolution, was published, followed by Lenz (first partly published in Karl Gutzkow's and Wienberg's Deutsche Revue, which was banned soon). In 1836 his second play, Leonce and Lena, followed (about the nobility). His unfinished and most famous play, Woyzeck, was published posthumously. It is the first literary work in German whose main characters are members of the working class. Büchner was one of the lesser known German authors when Karl-Emil Franzos edited his works, which later on were a major influence on naturalism. Arnold Zweig called Lenz, Büchner's only work of prose, the "beginning of modern European prose". Lenz is a novella based on the life of the Sturm und Drang poet Jakob Michael Reinhold Lenz.
He died in Zürich, shortly after he had begun lecturing at the university.