He studied in the Brussels Military Academy and the Cavalry School at Ypres, joining the Hellenic Army in 1906 as a Cavalry 2nd Lieutenant.

In the First Balkan War he served as a junior officer in the General Staff of King Constantine. As a captain, he held successive staff positions as well as taking part in the Siege of Yannina (Ioannina) and fighting in Macedonia from November 1912 until March 1913. He was a confirmed royalist, so when the King was deposed in 1917, he was dismissed from the Army along with many other officers. He was recalled after the return of King Constantine in 1920.

He served as operations officer to the Cavalry Brigade in the disastrous Asia Minor Campaign and was decommissioned after the ruling government was forced out by a revolutionary council headed by Nikolaos Plastiras. He was again recalled in 1927 with the rank of Major General and promoted to Lieutenant General in 1931 and Corps Commander in 1934. In October 1935, as a Lieutenant General and Chief of the Army, along with the chiefs of the Navy and the Air Force, he helped topple the government of Panagis Tsaldaris and declared the restoration of the monarchy, allowing for the return of King George II. He was appointed Minister of War in the Georgios Kondylis, Konstantinos Demertzis and Ioannis Metaxas governments. From his position, he employed the Army to support Metaxas' declaration of dictatorship in 4 August 1936.

During the next years, as Chief of the General Staff, he actively tried to reorganize and reequip the Army for the oncoming war. At the outbreak of the Greco - Italian War on October 28, 1940, he was Commander - in - Chief and directed Greek operations against Italy along the Greek - Albanian border. The Greek army, under his command, managed to halt the Italian advance by 8 November and forced them to withdraw deep into Albania between 18 November and 23 December. The successes of the Greek Army brought him fame and applause. Time Magazine placed him on its cover, as Papagos 'Commander of the Greeks' on 10 December 1949. A second Italian offensive between 9 and 16 March 1941 was repulsed. Despite this success, Papagos was forced to maintain the bulk of the Greek Army in Albania, and was unwilling to order a gradual withdrawal to reinforce the north - eastern border as German intervention came closer.

After the German invasion on 6 April 1941, outnumbered Greek forces in Macedonia fiercely resisted the German offensive at the so called Metaxas Line, but were outflanked and Papagos endorsed their surrender. Soon after the Army of Epirus capitulated and by 23 April the Greek government was forced to flee to Crete. Papagos remained behind and in July 1943, together with other generals, he was arrested and sent to concentration camps in Germany. In late April 1945 he was transferred to Tyrol together with about 140 other prominent inmates of the Dachau concentration camp, where the SS left the prisoners behind. He was liberated by the Fifth U.S. Army on 5 May 1945.

In 1945 he returned to Greece, rejoined the Army and reached the rank of full General in 1947. In August 1945, he was appointed an Honorary Knight Grand Cross of the Order of the British Empire by the British. On 29 January 1949, he was once again appointed Commander - in - Chief, to defeat the Communists in the Greek Civil War. This he achieved, with extensive American aid, including napalm equipped aircraft, and the extensive deployment of Special Forces (LOK), during the Grammos - Vitsi campaign between February to October of that year. As a reward for his services, he was awarded the title of Marshal on 28 October 1949. His is the only Greek career officer to ever hold this rank.

He continued to serve in his capacity as Commander - in - Chief until 1951, while Greece was in a state of political instability, with splinter parties and weak politicians unable to provide a firm government.

In May 1951 he resigned from the Army in order to become involved in politics. He founded the Greek Rally (Ελληνικός Συναγερμός), modelled after De Gaulle's Rassemblement du Peuple Français and won the September elections with 36.53 percent of the vote, largely due to his popularity, his image as a strong and determined leader, and the communist defeat in the civil war, which was attributed in great part to his leadership. Despite this victory, Papagos was unable to form a government on this majority, and had to wait until the November 1952 elections, where his party tallied an impressive 49 percent of the popular vote, gaining 239 out of 300 seats in Parliament. The Field Marshal, with his popular backing and support from the Americans was an authoritative figure, leading to friction with the Royal Palace. Papagos' government successfully strived to modernize Greece (where the young and energetic Minister of Public Works, Constantine Karamanlis, first distinguished himself) and restore the economy of a country ruined by 10 years of war, but was criticized by the opposition for doing little to restore social harmony in a country still scarred from the civil war.

One of the major issues faced by Papagos was the Cyprus problem, where the Greek majority had begun clamouring for Enosis (Union) with Greece. In response to demonstrations in the streets of Athens, Papagos reluctantly, as this would put Greece in confrontation with Great Britain, ordered Greece's UN representative in August 1954 to raise the issue of Cyprus before the UN General Assembly. When the EOKA armed struggle began in 1955, Papagos was in declining health and unwilling to act. The clashes in Cyprus, however, led to a deterioration of Greco - Turkish relations, culminating in the Istanbul Pogrom in September. By that time, Papagos was ill, and on 4 October 1955, he died.

The Athens suburb of Papagou, where the Ministry of Defence is located, is named after him.