Szent-Györgyi was born in Budapest, Kingdom of Hungary, Austro-Hungarian Empire, in 1893. His father, Miklós Szent-Györgyi, was a landowner, born in Marosvásárhely, Transylvania (today Târgu Mureş, Romania), a Calvinist, and could trace his ancestry back to 1608 when Sámuel, a Calvinist predicant, was ennobled. At the time of Szent-Györgyi's birth, being of the nobility was considered important and created opportunities that otherwise were not available. (Miklós Szent-Györgyi's parents were Imre Szent-Györgyi and Mária Csiky). His mother, Jozefina, a Roman Catholic, was a daughter of József Lenhossék and Anna Bossányi. Jozefina was a sister of Mihály Lenhossék; both of these men were Professors of Anatomy at the Eötvös Loránd University. His family included three generations of Scientists. Music was important in the Lenhossék family. His mother Jozefina prepared to become an opera singer and auditioned for Gustav Mahler, then a Conductor at the Budapest Opera. He advised her to marry instead, since her voice was not enough. Albert himself was good at the piano, while his brother Pál became a professional Violinist.

Szent-Györgyi began his studies at the Semmelweis University in 1911, then began research in his uncle's anatomy lab. His studies were interrupted in 1914 to serve as an army medic in World War I. In 1916, disgusted with the war, Szent-Györgyi shot himself in the arm, claimed to be wounded from enemy fire, and was sent home on medical leave. He was then able to finish his medical education and received his MD in 1917. He married Kornélia Demény, the daughter of the Hungarian Postmaster General, that same year.

He married Cornelia Demény, daughter of the Hungarian Postmaster-General, in 1917. Their daughter, Cornelia Szent-Györgyi, was born in 1918. He and Cornelia divorced in 1941.

After the war, Szent-Györgyi began his research career in Bratislava. He switched universities several times over the next few years, finally ending up at the University of Groningen, where his work focused on the chemistry of cellular respiration. This work landed him a position as a Rockefeller Foundation fellow at Cambridge University. He received his PhD from Fitzwilliam College, Cambridge in 1927 for work on isolating an organic acid, which he then called "hexuronic acid", from adrenal gland tissue.

He accepted a position at the University of Szeged in 1930. There, Szent-Györgyi and his research fellow Joseph Svirbely found that "hexuronic acid" was actually the thus far unidentified antiscorbutic factor, known as vitamin C. After Walter Norman Haworth had determined the structure of vitamin C, and in honour of its antiscorbutic properties, it was given the formal chemical name of L-ascorbic acid. In some experiments they used paprika as the source for their vitamin C. Also during this time, Szent-Györgyi continued his work on cellular respiration, identifying fumaric acid and other steps in what would become known as the Krebs cycle. In Szeged he also met Zoltán Bay, Physicist, who became his personal friend and partner in research on matters of bio-physics.

In 1937, he received the Nobel Prize in Physiology or Medicine "for his discoveries in connection with the biological combustion process with special reference to vitamin C and the catalysis of fumaric acid". Albert Szent-Györgyi offered all of his Nobel prize money to Finland in 1940. (The Hungarian Volunteers in the Winter War travelled to fight for the Finns after the Soviet invasion of Finland in 1939.)

In 1938, he began work on the biophysics of muscle movement. He found that muscles contain actin, which when combined with the protein myosin and the Energy source ATP, contract muscle fibers.

In 1941, he wed Marta Borbiro Miskolczy. She died of cancer in 1963.

As the government of Gyula Gömbös and the associated Hungarian National Defence Association gained control of politics in Hungary, Szent-Györgyi helped his Jewish friends escape from the country. During World War II, he joined the Hungarian resistance movement. Although Hungary was allied with the Axis Powers, the Hungarian prime minister Miklós Kállay sent Szent-Györgyi to Cairo in 1944 under the guise of a scientific lecture to begin secret negotiations with the Allies. The Germans learned of this plot and Adolf Hitler himself issued a warrant for the arrest of Szent-Györgyi. He escaped from house arrest and spent 1944 to 1945 as a fugitive from the Gestapo.

After the war, Szent-Györgyi had become well-recognized as a public figure and there was some speculation that he might become President of Hungary, should the Soviets permit it. Szent-Györgyi established a laboratory at the University of Budapest and became head of the biochemistry department there. He was elected a member of Parliament and helped re-establish the Academy of Sciences. Dissatisfied with the Communist rule of Hungary, he emigrated to the United States in 1947.

In the late 1950s, Szent-Györgyi developed a research interest in cancer and developed ideas on applying the theories of quantum mechanics to the biochemistry (quantum biology) of cancer. The death of Rath, who had acted as the financial administrator of the Institute for Muscle Research, left Szent-Györgyi in a financial mess. Szent-Györgyi refused to submit government grants which required him to provide minute details on exactly how he intended to spend the research dollars and what he expected to find. After Szent-Györgyi commented on his financial hardships in a 1971 newspaper interview, attorney Franklin Salisbury contacted him and later helped him establish a private nonprofit organization, the National Foundation for Cancer Research. Late in life, Szent-Györgyi began to pursue free radicals as a potential cause of cancer. He came to see cancer as being ultimately an electronic Problem at the molecular level. In 1974, reflecting his interests in quantum physics, he proposed the term "syntropy" replace the term "negentropy". Ralph Moss, a protégé of his in the years he performed his cancer research, wrote a biography entitled: "Free Radical: Albert Szent-Gyorgyi and the Battle over Vitamin C", ISBN 0-913729-78-7, (1988), Paragon House Publishers, New York. Aspects of this work are an important precursor to what is now dubbed redox signaling.

Szent-Györgyi married June Susan Wichterman, the 25-year-old daughter of Woods Hole Biologist Ralph Wichterman, in 1965. They were divorced in 1968.

In 1967, Szent-Györgyi signed a letter declaring his intention to refuse to pay taxes as a means of protesting against the U.S. war against Vietnam, and urging other people to take a similar stand.

He married his fourth wife, Marcia Houston, in 1975. They adopted a daughter, Lola von Szent-Györgyi.

Szent-Györgyi died in Woods Hole, Massachusetts, USA on October 22, 1986. He was honored with a Google Doodle September 16, 2011, 118 years after his birth. In 2004, nine interviews were conducted with family, colleagues, and others to create a Szent-Györgyi oral history collection.