Hess, the oldest of three children, was born on 26 April 1894 in Alexandria, Egypt, into the ethnic German family of Fritz Hess, a prosperous merchant from Bavaria, and Clara Hess (née Münch). His brother, Alfred, was born in 1897 and his sister, Margarete, was born in 1908. The family lived in a villa on the Egyptian coast near Alexandria, and visited Germany often from 1900, staying at their summer home in Reicholdsgrün (now part of Kirchenlamitz) in the Fichtel Mountains. Hess attended a German language Protestant school in Alexandria from 1900 to 1908, when he was sent back to Germany to study at a boarding school in Bad Godesberg. He demonstrated aptitudes for science and mathematics, but his father wished him to join the family Business, Hess & Co., so he sent him in 1911 to study at the École supérieure de commerce in Neuchâtel, Switzerland. After a year there, Hess took an apprenticeship at a trading company in Hamburg.

Within weeks of the outbreak of World War I, Hess enlisted in the 7th Bavarian Field Artillery Regiment. His initial posting was against the British on the Somme; he was present at the First Battle of Ypres. On 9 November 1914 Hess transferred to the 1st Infantry Regiment, stationed near Arras. He was awarded the Iron Cross, second class, and promoted to Gefreiter (corporal) in April 1915. After additional training at the Munster Training Area, he was promoted to Vizefeldwebel (senior non-commissioned officer) and received the Bavarian Military Merit Cross. Returning to the front lines in November, he fought in Artois, participating in the battle for the town of Neuville-Saint-Vaast. After two months out of action with a throat infection, Hess served in the Battle of Verdun in May, and was hit by shrapnel in the left hand and arm on 12 June 1916 in fighting near the village of Thiaumont. After a month off to recover, he was sent back to the Verdun area, where he remained until December.

Hess enlisted as an infantryman at the outbreak of World War I. He was wounded several times over the course of the war and was awarded the Iron Cross, 2nd class, in 1915. Shortly before the war ended, Hess enrolled to train as an aviator, but he saw no action in this role. He left the armed forces in December 1918 with the rank of Leutnant der Reserve.

Hess was promoted to platoon leader of the 10th Company of the 18th Bavarian Reserve Infantry Regiment, which was serving in Romania. He was wounded on 23 July and again on 8 August 1917; the first injury was a shell splinter to the left arm, which was dressed in the field, but the second was a bullet wound that entered the upper chest near the armpit and exited near his spinal column, leaving a pea-sized entry wound and a cherry stone-sized exit wound on his back. By 20 August he was well enough to travel, so he was sent to hospital in Hungary and eventually back to Germany, where he recovered in hospital in Meissen. In October he received promotion to Leutnant der Reserve and was recommended for, but did not receive, the Iron Cross, first class. At his father's request, Hess was transferred to a hospital closer to home, arriving at Alexandersbad on 25 October.

Hess was discharged from the armed forces in December 1918. The family fortunes had taken a serious downturn, as their Business interests in Egypt had been expropriated by the British. Hess joined the Thule Society, an antisemitic right-wing Völkisch group, and a Freikorps, one of many such volunteer paramilitary organisations active in Germany at the time. Bavaria witnessed frequent and often bloody conflicts between right-wing groups such as the Freikorps and left-wing forces as they fought for control of the state during this period. Hess was a participant in street battles in early 1919 and led a group which distributed thousands of antisemitic pamphlets in Munich. He later said that Egypt made him a nationalist, the war made him a socialist, and Munich made him an antisemite.

In 1919, Hess enrolled in the University of Munich, where he studied history and economics. His geopolitics professor was Karl Haushofer, a proponent of the concept of Lebensraum ("living space"), which Haushofer cited to justify the proposal that Germany should forcefully conquer additional territory in Eastern Europe. Hess later introduced this concept to Adolf Hitler, and it became one of the pillars of Nazi Party ideology. Hess became friends with Haushofer and his son Albrecht, a social theorist and lecturer.

In 1919, Hess enrolled in the University of Munich, where he studied geopolitics under Karl Haushofer, a proponent of the concept of Lebensraum ("living space"), which later became one of the pillars of Nazi Party (NSDAP) ideology. Hess joined the NSDAP on 1 July 1920, and was at Hitler's side on 8 November 1923 for the Beer Hall Putsch, a failed Nazi attempt to seize control of the government of Bavaria. Whilst serving time in jail for this attempted coup, Hess helped Hitler write his book, Mein Kampf, which became a foundation of the political platform of the NSDAP.

After hearing NSDAP leader Hitler speak for the first time in 1920 at a Munich rally, Hess became completely devoted to him. They held a shared belief in the stab-in-the-back myth, the notion that Germany's loss in World War I was caused by a conspiracy of Jews and Bolsheviks rather than a military defeat. Hess joined the NSDAP on 1 July as member number 16. As the party continued to grow, holding rallies and meetings in ever larger beer halls in Munich, he focused his attention on fundraising and organisational activities. On 4 November 1921 he was injured while protecting Hitler when a bomb planted by a Marxist group exploded at the Hofbräuhaus during a party event. Hess joined the Sturmabteilung (SA) by 1922 and helped organise and recruit its early membership.

Meanwhile, problems continued with the economy; hyperinflation caused many personal fortunes to be rendered worthless. When the German government failed to meet its reparations payments and French troops marched in to occupy the industrial areas along the Ruhr in January 1923, widespread civil unrest was the result. Hitler decided the time was ripe to attempt to seize control of the government with a coup d'état modelled on Benito Mussolini's 1922 March on Rome. Hess was with Hitler on the night of 8 November 1923 when he and the SA stormed a public meeting organised by Bavaria's de facto ruler, Staatskommissar (state commissioner) Gustav von Kahr, in the Bürgerbräukeller, a large beer hall in Munich. Brandishing a pistol, Hitler interrupted Kahr's speech and announced that the national revolution had begun, declaring the formation of a new government with World War I General Erich Ludendorff. The next day, Hitler and several thousand supporters attempted to march to the Ministry of War in the city centre. Gunfire broke out between the Nazis and the police; fourteen marchers and four police officers were killed. Hitler was arrested on 11 November.

Hitler was released on parole on 20 December 1924 and Hess ten days later. The ban on the NSDAP and SA was lifted in February 1925, and the party grew to 100,000 members in 1928 and 150,000 in 1929. They received only 2.6 per cent of the vote in the 1928 election, but support increased steadily up until the seizure of power in 1933.

Both men were incarcerated in Landsberg Prison, where Hitler soon began work on his memoir, Mein Kampf ("My Struggle"), which he dictated to fellow prisoners Hess and Emil Maurice. Edited by publisher Max Amann, Hess and others, the work was published in two parts in 1925 and 1926. It was later released in a single volume, which became a best-seller after 1930. This book, with its message of violent antisemitism, became the foundation of the political platform of the NSDAP.

Ilse Pröhl, a fellow student at the university, met Hess in April 1920 when they by chance rented rooms in the same boarding house. They married on 20 December 1927 and their son Wolf Rüdiger Hess was born ten years later, in 1937.

Retaining his interest in flying after the end of his active military career, Hess obtained his private pilot's licence on 4 April 1929. His instructor was World War I flying ace Theodor Croneiss. In 1930 Hess became the owner of a BFW M.23b monoplane sponsored by the party newspaper, the Völkischer Beobachter. He acquired two more Messerschmitt aircraft in the early 1930s, logging many flying hours and becoming proficient in the operation of light single-engine aircraft.

On 30 January 1933, Hitler was appointed Reich Chancellor, his first step in gaining dictatorial control of Germany. Hess was named Deputy Führer of the NSDAP on 21 April and was appointed to the cabinet, with the post of Reich Minister without Portfolio, on 1 December. With offices in the Brown House in Munich and another in Berlin, Hess was responsible for several departments, including foreign affairs, Finance, health, education and law. All legislation passed through his office for approval, except that concerning the army, the police and foreign policy, and he wrote and co-signed many of Hitler's decrees. An organiser of the annual Nuremberg Rallies, he usually gave the opening speech and introduced Hitler. Hess also spoke over the radio and at rallies around the country, so frequently that the speeches were collected into book form in 1938. Hess acted as Hitler's delegate in negotiations with industrialists and members of the wealthier classes. As Hess had been born abroad, Hitler had him oversee the NSDAP groups such as the NSDAP/AO that were in charge of party members living in other countries. Hitler instructed Hess to review all court decisions that related to persons deemed enemies of the Party. He was authorised to increase the sentences of anyone he felt got off too lightly in these cases, and was also empowered to take "merciless action" if he saw fit to do so. This often entailed sending the person to a concentration camp or simply ordering the person killed. Hess was given the rank of Obergruppenführer in the Schutzstaffel (SS) in 1934, the second-highest SS rank.

Hess was interested in music, enjoyed reading and loved to spend time hiking and climbing in the mountains with Ilse. He and his friend Albrecht Haushofer shared an interest in astrology, and Hess also was keen on clairvoyance and the occult. Hess continued to be interested in aviation. He won an air race in 1934, flying a BFW M.35 in a circuit around Zugspitze Mountain and returning to the airfield at Munich with a time of 29 minutes. He placed sixth of 29 participants in a similar race held the following year. With the outbreak of World War II, Hess asked Hitler to be allowed to join the Luftwaffe as a pilot, but Hitler forbade it, and ordered him to stop flying for the duration of the war. Hess convinced him to reduce the ban to one year.

The Nazi regime began to persecute Jews soon after the seizure of power. Hess's office was partly responsible for drafting Hitler's Nuremberg Laws of 1935, laws that had far-reaching implications for the Jews of Germany, banning marriage between non-Jewish and Jewish Germans and depriving non-Aryans of their German citizenship. Hess's friend Karl Haushofer and his family were subject to these laws, as Haushofer had married a half-Jewish woman, so Hess issued documents exempting them from this legislation.

Hess did not build a power base or develop a coterie of followers. He was motivated by his loyalty to Hitler and a Desire to be useful to him; he did not seek power or prestige or take advantage of his position to accumulate personal wealth. He lived in a modest house in Munich. Although Hess had less influence than other top NSDAP officials, he was popular with the masses. After the Invasion of Poland and the start of World War II in September 1939, Hitler made Hess second in line to succeed him, after Hermann Göring. Around the same time, Hitler appointed Hess's chief of staff, Martin Bormann, as his personal secretary, a post formerly held by Hess.

A letter Hess wrote to his wife dated 4 November 1940 shows that in spite of not receiving a reply from Hamilton, he intended to proceed with his plan. He began training on the Messerschmitt Bf 110, a two-seater twin-engine aircraft, in October 1940 under instructor Wilhelm Stör, the chief test pilot at Messerschmitt. He continued to practise, including logging many cross-country flights, and found a specific aircraft that handled well—a Bf 110E-1/N—which was from then on held in reserve for his personal use. He asked for a radio compass, modifications to the oxygen delivery system, and large long-range fuel tanks to be installed on this plane, and these requests were granted by March 1941.

The wreckage of the aircraft was salvaged by 63 Maintenance Unit between 11 and 16 May 1941 and was taken to Oxford to be stored. The aeroplane was armed with four machine guns in the nose but carried no ammunition. Several pieces of the plane still exist, including the two engines and a piece of the fuselage.

Hess was moved to Maindiff Court Hospital on 26 June 1942, where he remained for the next three years. The facility was chosen for its added security and the need for fewer guards. Hess was allowed walks on the grounds and car trips into the surrounding countryside. He had access to newspapers and other reading materials; he wrote letters and journals. His mental health remained under the care of Dr Rees. Hess continued to complain on and off of memory loss and made a second suicide attempt on 4 February 1945, when he stabbed himself with a bread knife. The wound was not serious, requiring two Stitches. Despondent that Germany was losing the war, he took no food for the next week, only resuming eating when he was threatened with being force-fed.

American Journalist H. R. Knickerbocker, who had met both Hitler and Hess, speculated that Hitler had sent Hess to deliver a message informing Winston Churchill of the forthcoming invasion of the Soviet Union, and offering a negotiated peace or even an anti-Bolshevik partnership. Soviet leader Joseph Stalin believed that Hess's FLIGHT had been engineered by the British. Stalin persisted in this belief as late as 1944, when he mentioned the matter to Churchill, who insisted that they had no advance knowledge of the FLIGHT.

The Allies of World War II held a series of military tribunals and trials, beginning with a trial of the major war Criminals from November 1945 to October 1946. Hess was tried with this first group of 23 defendants, all of whom were charged with four counts—conspiracy to commit crimes, crimes against peace, war crimes and crimes against humanity, in violation of international laws governing warfare.

The prosecution's case against Hess was presented by Mervyn Griffith-Jones beginning on 7 February 1946. By quoting from Hess's speeches, he attempted to demonstrate that Hess had been aware of and agreed with Hitler's plans to conduct a war of aggression in violation of international law. He declared that as Hess had signed important governmental decrees, including the decree requiring mandatory military Service, the Nuremberg racial laws, and a decree incorporating the conquered Polish territories into the Reich, he must share responsibility for the acts of the regime. He pointed out that the timing of Hess's trip to Scotland, only six weeks before the Nazi invasion of the Soviet Union, could only be viewed as an attempt by Hess to keep the British out of the war. Hess resumed showing symptoms of amnesia at the end of February, partway through the prosecution's case.

Numerous appeals for Hess's release were launched by his Lawyer, Dr Alfred Seidl, beginning as early as 1947. These were denied, mainly because the Soviets repeatedly vetoed the proposal. Spandau was located in West Berlin, and its existence gave the Soviets a foothold in that sector of the city. Additionally, Soviet officials believed Hess must have known in 1941 that an attack on their country was imminent. In 1967, Wolf Rüdiger Hess began a campaign to win his father's release, garnering support from notable politicians such as Geoffrey Lawrence, 1st Baron Oaksey in Britain and Willy Brandt in Germany, but to no avail, in spite of the prisoner's advanced age and deteriorating health.

Other than his stays in hospital, Hess spent the rest of his life in Spandau Prison. His fellow inmates Konstantin von Neurath, Walther Funk and Erich Raeder were released because of poor health in the 1950s; Karl Dönitz, Baldur von Schirach, and Albert Speer served their time and were released; Dönitz in 1956, Schirach and Speer in 1966. The 600-cell prison continued to be maintained for its lone prisoner from Speer and Schirach's release until Hess's death in 1987, at an estimated cost of DM 800,000. Conditions were far more pleasant in the 1980s than in the early years; Hess was allowed to move more freely around the cell block, setting his own routine and choosing his own activities, which included television, films, reading and gardening. A lift was installed so he could more readily access the garden, and he was provided with a medical orderly from 1982 onward.

Visits to Spandau of half an hour per month were allowed, but Hess forbade his family to visit until December 1969, when he was a patient at the British Military Hospital in West Berlin for a perforated ulcer. By this time Wolf Rüdiger Hess was 32 years old and Ilse 69; they had not seen Hess since his departure from Germany in 1941. After this illness, he allowed his family to visit regularly. His daughter-in-law Andrea, who often brought photos and films of his grandchildren, became a particularly welcome visitor. Hess's health problems, both mental and physical, were ongoing during his captivity. He cried out in the night, claiming he had stomach pains. He continued to suspect that his food was being poisoned and complained of amnesia. A Psychiatrist who examined him in 1957 deemed he was not ill enough to be transferred to a mental hospital. Another unsuccessful suicide attempt took place in 1977.

His Lawyer, Dr Alfred Seidl, felt Hess was too old and frail to have managed to kill himself. Wolf Rüdiger Hess repeatedly claimed that his father had been murdered by the British Secret Intelligence Service to prevent him from revealing information about British misconduct during the war. Abdallah Melaouhi, who served as Hess's medical orderly from 1982 to 1987, was dismissed from his position at his local district parliament's Immigration and Integration Advisory Council after he wrote a self-published book on a similar theme. According to an investigation by the British government in 1989, the available evidence did not back up the claim that Hess was murdered, and Solicitor General Sir Nicholas Lyell saw no grounds for further investigation. Moreover, the autopsy results support the conclusion that Hess had killed himself. A report released in 2012 again raised the question of whether Hess was murdered. Historian Peter Padfield claims the suicide note found on the body appears to have been written when Hess was hospitalised in 1969.

Hess died on 17 August 1987 at the age of 93 in a summer house that had been set up in the prison garden as a reading room. He took an extension cord from one of the lamps, strung it over a window latch, and hanged himself. Death occurred by asphyxiation. A short note to his family, thanking them for all they had done, was found in his pocket. The Four Powers released a statement on 17 September ruling the death a suicide. Initially buried at a secret location to avoid media attention or demonstrations by Nazi sympathisers, Hess was re-interred in a family plot at Wunsiedel on 17 March 1988, and his wife was buried beside him when she died in 1995. Spandau Prison was demolished to prevent it from becoming a neo-Nazi shrine.

After the town of Wunsiedel became the scene of pilgrimages and neo-Nazi demonstrations every August on the date of Hess's death, the parish council decided not to allow an extension on the grave site's lease when it expired in 2011. With the eventual consent of his family, Hess's grave was re-opened on 20 July 2011 and his remains were exhumed, and then cremated. His ashes were scattered at sea by family members; the gravestone, which bore the epitaph "Ich hab's gewagt" ("I have dared"), was destroyed.

The case for Hess's defence was presented from 22–26 March by his Lawyer, Dr Alfred Seidl. He noted that while Hess accepted responsibility for the many decrees he had signed, he said these matters were part of the internal workings of a sovereign state and thus outside the purview of a war crimes trial. He called to the stand Ernst Wilhelm Bohle, the man who had been head of the NSDAP/AO, to testify on Hess's behalf. When Griffith-Jones presented questions about the organisation's spying in several countries, Bohle testified that any warlike activities such as espionage had been done without his permission or knowledge. Seidl called two other witnesses, former mayor of Stuttgart Karl Strölin and Hess's brother Alfred, both of whom refuted the allegations that the NSDAP/AO had been spying and fomenting war. Seidl presented a summation of the defence's case on 25 July, in which he attempted to refute the charge of conspiracy by pointing out that Hitler alone had made all the important decisions. He noted that Hess could not be held responsible for any events that took place after he left Germany in May 1941. Meanwhile, Hess mentally detached himself from what was happening, declining visits from his family and refusing to read the newspapers.

Spandau was placed under the control of the Allied Control Council, the governing body in charge of the military occupation of Germany. It consisted of representatives from four member states: Britain, France, the United States and the Soviet Union. Each country supplied guards for the prison for a month at a time on a rotating basis. After the inmates were given medical examinations—Hess refused his body search, and had to be held down—they were provided with prison garb and assigned the numbers by which they would be addressed throughout their stay. Hess was Number 7. The prison had a small library, and inmates were allowed to file special requests for additional reading material. Writing materials were limited; each inmate would be allowed four pieces of paper per month for letters. The prisoners were not allowed to speak to one another without permission and were expected to work in the facility, helping with cleaning and gardening chores. The inmates were taken for outdoor walks around the prison grounds for an hour each day, separated about 10 yards (9 m) apart. Some of the rules became more relaxed as time went on.