Borden was a Liberal until he broke with the party in 1891 over the issue of Reciprocity.

He was elected to Parliament in the 1896 federal election as a Conservative and in 1901 was selected by the Conservative caucus to succeed Sir Charles Tupper as leader of the Conservative Party. Over the next decade he worked to rebuild the party and establish a reform policy, the Halifax Platform of 1907 which he described as "the most advanced and progressive policy ever put forward in Federal affairs". It called for reform of the Senate and the civil service, a more selective immigration policy, free rural mail delivery, and government regulation of telegraphs, telephones, and railways and eventually national ownership of telegraphs and telephones. Despite his efforts, his party lost the 1908 federal election to Wilfrid Laurier's Liberals. His party's fortunes turned around in the 1911 federal election, however, when the Conservatives successfully campaigned against Laurier's proposals for a Reciprocity (free trade) agreement with the United States. Borden countered with a revised version of John A. Macdonald's National Policy and appeals of loyalty to the British Empire and ran on the slogan "Canadianism or Continentalism". In British Columbia, the party ran on the slogan "A White Canada," playing to the racist fears of white British Columbians that resented the increasing presence of Asian immigrants. In Quebec, concurrently, Henri Bourassa led a campaign against what he saw as Laurier's capitulation to British imperialism, playing a part in the defeat of Laurier's government and the election of Borden's Tories.

As Prime Minister of Canada during the First World War, Borden transformed his government to a wartime administration, passing the War Measures Act in 1914. Borden committed Canada to provide half a million soldiers for the war effort. However, volunteers had quickly dried up when Canadians realized there would be no quick end to the war. Borden's determination to meet that huge commitment led to the Military Service Act and the Conscription Crisis of 1917, which split the country on linguistic lines. The unpopular conscription issue would likely have meant defeat in the election of 1917, but Borden recruited members of the Liberals (with the notable exception of Wilfrid Laurier) to create a Unionist government. The 1917 election saw the "Government" candidates (including a number of Liberal-Unionists) crush the Opposition "Laurier Liberals" in English Canada resulting in a large parliamentary majority for Borden. The war effort also enabled Canada to assert itself as an independent power. Borden wanted to create a single Canadian army, rather than have Canadian soldiers split up and assigned to British divisions as had happened during the Boer War. Sam Hughes, the Minister of Militia, generally ensured that Canadians were well-trained and prepared to fight in their own divisions, although with mixed results such as the Ross Rifle. Arthur Currie provided sensible leadership for the Canadian divisions in Europe, although they were still under overall British command. Nevertheless Canadian troops proved themselves to be among the best in the world, fighting at the Somme, Ypres, Passchendaele, and especially at the Battle of Vimy Ridge.

During Borden's first term as prime minister, the National Research Council of Canada was established in 1916.

In world affairs, Borden played a crucial role in transforming the British Empire into a partnership of equal states, the Commonwealth of Nations, a term that was first discussed at an Imperial Conference in London during the war. Borden also introduced the first Canadian income tax, which at the time was meant to be temporary, but was never repealed. Convinced that Canada had become a nation on the battlefields of Europe, Borden demanded that it have a separate seat at the Paris Peace Conference. This was initially opposed not only by Britain but also by the United States, who perceived such a delegation as an extra British vote. Borden responded by pointing out that since Canada had lost more men than the U.S. in the war, she at least had the right to the representation of a "minor" power. British Prime Minister David Lloyd George eventually relented, and convinced the reluctant Americans to accept the presence of separate Canadian, Indian, Australian, Newfoundland, New Zealand and South African delegations. Despite this, Borden boycotted the opening ceremony, protesting at the precedence given to the prime minister of the much smaller Newfoundland over him. Not only did Borden's persistence allow him to represent Canada in Paris as a nation, it also ensured that each of the dominions could sign the Treaty of Versailles in its own right, and receive a separate membership in the League of Nations. During the conference Borden tried to act as an intermediary between the United States and other members of the British Empire delegation, particularly Australia and New Zealand over the issue of Mandates. Borden also discussed with Lloyd George, the possibility of Canada taking over the administration of Belize and the West Indies, but no agreement was reached. At Borden's insistence, the treaty was ratified by the Canadian Parliament. Borden was the last prime minister to be knighted after the House of Commons indicated its desire for the discontinuation of the granting of any future titles to Canadians in 1919 with the adoption of the Nickle Resolution.

That same year, Borden approved the use of troops to put down the Winnipeg General Strike, which was feared to be the result of Bolshevik agitation from the Soviet Union.

Sir Robert Borden retired from office in 1920. He was the Chancellor of Queen's University from 1924 to 1930 and also was Chancellor of McGill University from 1918 to 1920 while still Prime Minister. At his death he stood as president of two financial institutions Barclay's Bank of Canada and the Crown Life Insurance Company. Borden died on 10 June 1937 in Ottawa and is buried in the Beechwood Cemetery marked by a simple stone cross.