Windthorst was born at Kaldenhof, a country house near Osnabrück in the Kingdom of Hanover. He was raised by a Roman Catholic family, which for some generations had held important posts in the Hanoverian civil service. He was educated at the Carolinum, an endowed school at Osnabrück, and studied at the universities of Göttingen and Heidelberg.
In 1836, Windthorst settled down as an advocate in Osnabrück: his abilities soon procured him a considerable practice, and he was appointed president of the Catholic Consistorium. In 1848, he received an appointment at the supreme court of appeal for the kingdom of Hanover, which sat at Celle. In the next year, the revolution opened for him—as for so many of his contemporaries—the way to public life, and he was elected representative for his native district in the second chamber of the reformed Hanoverian parliament. He belonged to what was called the Great German party, and opposed the project of reconstituting Germany under the leadership of the Kingdom of Prussia He defended the government against the liberal and democratic opposition; and, at this time, he began his struggle against the secularization of schools, which continued throughout his life.
In 1851, he was elected president of the chamber and, in the same year, minister of justice, the first Catholic who had held so high an office in Hanover. As minister, he carried through an important judicial reform—which had been prepared by his predecessor—but had to retire from office because he was opposed to the reactionary measures for restoring the influence and privileges of the nobility. Though he was always an enemy to liberalism, his natural independence of character prevented him from acquiescing in the reactionary measures of the king. In 1862, he again was appointed minister, but with others of his colleagues, he resigned when the king refused his assent to a measure for extending the franchise. Windthorst took no part in the critical Austro-Prussian War; contrary to the opinion of many of his friends, after the annexation of Hanover by Prussia, he accepted the fait accompli, took the oath of allegiance, and was elected a member both of the Prussian parliament and of the North German diet.
At Berlin, he found a wider field for his abilities. He acted as representative of his exiled king in the negotiations with the Prussian government concerning his private property, and opposed the sequestration, and for the first time was placed in a position of hostility to Otto von Bismarck. He was recognized as the leader of the Hanoverians and of all those above who opposed the revolution. He took a leading part in the formation of the party of the Center in 1870–1871, but he did not become a member of it, for he feared that his reputation as a follower of the king of Hanover would injure the party; that is, until the leaders formally requested that he join them.
After the death of Hermann von Mallinckrodt (1821–1874) in 1874, Windthorst became leader of the party and maintained that position until his death. It was chiefly owing to his skill and courage as a parliamentary debater and his tact as a leader, that the party held its own and constantly increased in numbers during the great struggle with the Prussian government. He was especially exposed to the attacks of Bismarck, who attempted, personally, to discredit him and to separate him from the rest of the party. And, he was by far the ablest and most dangerous critic of Bismarck's policy. The change of policy in 1879 led to a great alteration in his position: he was reconciled to Bismarck and even sometimes attended receptions at Bismarck's house. Never, however, was his position so difficult as during the negotiations which led to a repeal of the May laws.
In 1887, Bismarck appealed to the Pope to use his authority to order the Center to support the military proposals of the government. Windthorst took the responsibility of keeping the papal instructions secret from the rest of his party and of disobeying the instructions. In a great meeting at Cologne in March 1887, he defended and justified his action, and claimed for the Center full independence of action in all purely political questions. In the social reform, he supported Bismarck, and as the undisputed leader of the largest party in the Reichstag, he was able to exercise influence over the action of the government after Bismarck's retirement. His relations with the emperor William II became very cordial, and in 1891 he achieved a great parliamentary triumph by defeating the School bill and compelling Gossler to resign. A few days afterwards he died, on March 14, 1891, at Berlin.
He was buried in the Marienkirche in Hanover, which had been erected from the money subscribed as a testimonial to him. His funeral was a most remarkable display of public esteem, in which nearly all the ruling princes of Germany joined, and was a striking sign of the position to which, after twenty years of incessant struggle, he had raised his party. Windthorst was undoubtedly one of the greatest of German parliamentary leaders: no one equalled him in his readiness as a debater—his defective eyesight compelling him to depend entirely upon his memory. It was his misfortune that nearly all his life was spent in opposition, and he had no opportunity of showing his abilities as an administrator. He enjoyed unbounded popularity and confidence among the German Catholics, but he was in no way an ecclesiastic: he was at first opposed to the Vatican decrees of 1870, but quickly accepted them after they had been proclaimed. He was a very agreeable companion and a thorough man of the world, singularly free from arrogance and pomposity—owing to his small stature, he was often known as "die kleine Excellenz". He married in 1839: of his three children, two died before him; his wife survived him only a few months.
Windthorst's Ausgewählte Reden were published in three volumes (Osnabrück, 1901–1902).