Treitschke was born in Dresden. He was the son of an officer in the Saxon army who rose to be governor of Königstein and military governor of Dresden. Treitschke went deaf at a young age, and so was prevented from entering public service. After studying at the universities of Leipzig and Bonn, where he was a student of Friedrich Christoph Dahlmann, he established himself as a Privatdozent at Leipzig, lecturing on history and politics. At one point he became very popular with the students, but his political opinions made it impossible for the Saxon government to appoint him to a professorship.

At that time Treitschke was a strong Liberal; he hoped to see Germany united into a single state with a parliamentary government, and all the smaller states swept away. In one statement he said that "Every virile people has established colonial power. All great nations in the fullness of their strength have desired to set their mark upon barbarian lands and those who fail to participate in this great rivalry will play a pitiable role in time to come." This harsh statement reflects on his increasing aggressiveness of European nationalism after Otto von Bismarck's wars toward the unification of Germany. It also discusses the Social Darwinian theories of brutal competition among races. In essay published in 1862 Treitschke praised the "pitiless racial struggle" of Germans against Lithuanians, Poles and Old Prussians, he claimed that "magic" emaneted from "eastern German soil" which had been "fertilised" by "noble German blood". While his main objective was to give historical legitimisation to the germanising of Poles that found themselves under Prussian rule, the praise of a mythical genocide conducted by German ancestors against other national groups would eventually become a means of legitimising claims to further eastern territories.

In 1863 he was appointed professor at Freiburg; in 1866, at the outbreak of the Austro - Prussian War, his sympathies with the Kingdom of Prussia were so strong that he went to Berlin, became a Prussian subject, and was appointed editor of the Preussische Jahrbücher. His violent article, in which he demanded the annexation of the Kingdoms of Hanover and Saxony, and attacked with great bitterness the Saxon royal house, led to an estrangement from his father, a personal friend of the king. It was only equalled in its ill humour by his attacks on Bavaria in 1870. After holding appointments at Kiel and Heidelberg, he was made professor at Humboldt University in Berlin in 1874.

In 1871, Treitschke became a member of the Reichstag, and from that time till his death he was one of the most prominent figures in Berlin.

On Heinrich von Sybel's death Treitschke succeeded him as editor of the Historische Zeitschrift. He had outgrown his early Liberalism and become the chief panegyrist of the House of Hohenzollern. He made violent and influential attacks on all opinions and all parties which appeared in any way to be injurious to the rising power of Germany. He supported the government in its attempts to subdue by legislation the Socialists, Poles and Catholics (Kulturkampf).

As a strong advocate of colonial expansion Treitschke was a bitter enemy of the British Empire. He was to a large extent responsible for the chauvinistic anti-British feeling of the last years of the 19th century.

In the Reichstag Treitschke had originally been a member of the National Liberal Party, but in 1879 he was the first to accept the new commercial policy of Bismarck, and in his later years he joined the Moderate Conservatives, though his deafness prevented him from taking a prominent part in debate.

Treitschke was one of the few important public figures who supported antisemitic attacks which became prevalent from 1878 onwards. He accused German Jews of refusing to assimilate into German culture and society, and attacked the flow of Jewish immigrants from Russian Poland. Treitschke has often been misquoted (predominantly by the National Socialists and contemporary leftists) as having coined the phrase "Die Juden sind unser Unglück!" ("The Jews are our misfortune!") adopted as a motto by the Nazi publication Der Stürmer several decades later. He actually remarked, "Everywhere in Germany you hear the same phrase, 'The Jews are our misfortune.'" Because of his respected status, Treitschke's remarks aroused widespread controversy.

Treitschke was held in high regard by political elites of Prussia and Chancellor Bernhard von Bülow personaly declared that he kept a copy of von Treitschke's book for "several years" on his desk.

Treitschke approached history as a politician, and confined himself to those periods and characters in which great political problems were being worked out: above all, he was a patriotic historian, and he never wandered far from Prussia. His great achievement was the History of Germany in the Nineteenth Century. The first volume was published in 1879, and during the next sixteen years four more volumes appeared, but at his death he had only advanced to the year 1847. He also wrote biographical and historical essays, and essays on contemporary politics.

The most important essays were collected as Historische und politische Aufsatze. A selection from his more controversial writings was made under the title Zehn Jahre deutscher Kämpfe; in 1896 a new volume appeared, called Deutsche Kämpfe, neue Folge. After his death his lectures on political subjects were published under the title Politik. He brought out also in 1856 a short volume of poems called Vaterländische Gedichte, and another volume in the following year. His first works to be translated into English were two pamphlets on the war of 1870, What we demand from France (London, 1870), and The Baptism of Fire of the North German Confederation (1870).

Treitschke's students included Heinrich Class, Hans Delbrück, W.E.B. Du Bois, Otto Hintze, Max Lenz, Erich Marcks, Friedrich Meinecke, Karl Peters, Ludwig Schiemann, Gustav Schnürer, Georg Simmel and Friedrich von Bernhardi. During World War I, many writers in the West, particularly in Britain, blamed Bernhardi for creating attitudes among the political class of Germany that were seen as an incitement to war. A complete translation of both volumes of Treitschke's Politics was published in London in 1916. Politics also appeared in an abridged English translation edited by Hans Kohn and published in 1963.