Percy FitzPatrick was born in King William's Town, the eldest son of James Coleman FitzPatrick, who was a judge of the Supreme Court of the Cape Colony, and Jenny FitzGerald. Both were originally from Ireland. Two of James Coleman FitzPatrick's other sons were killed in action - Thomas in the Matabele Rebellion and George in the Second Anglo-Boer War (serving with the Imperial Light Horse).

James Percy FitzPatrick was first educated at Downside School near Bath, England, and later at St. Aidan's College at Grahamstown, South Africa.

After his father's death in 1880, Percy FitzPatrick left college in order to support his mother and her family. He travelled to the Eastern Transvaal goldfields in 1884, where he worked as a storeman, prospector's assistant and journalist as well as an ox-wagon transport-rider from the former Lourenço Marques to Lydenburg and Barberton. He later became editor of the Gold Fields News in Barberton. An account of FitzPatrick's adventures during this time, Jock of the Bushveld, was published in 1907.

He also authored The Transvaal from Within, which greatly influenced public opinion in Great Britain in the years leading up to the Anglo-Boer War. It emphasized Uitlander grievances and advocated British intervention in the South African Republic (ZAR).

In 1892 FitzPatrick became the head of intelligence in the Johannesburg offices of Hermann Eckstein and Company (part of Wernher-Beit and Company). FitzPatrick became the secretary of the Reform Committee in Johannesburg in 1895. The Committee conspired to overthrow Paul Kruger's South African Republic government from 1895 to 1896. FitzPatrick also acted as go-between the Committee and Cecil John Rhodes and Leander Starr Jameson in Cape Town. On 29 December 1895, Jameson led a failed raid from the Bechuanaland Protectorate (modern-day Botswana) to aid the conspirators in Johannesburg, but was stopped at Doornkop on 2 January 1896 Jameson Raid. FitzPatrick was charged with the others for high treason. Although sentenced to two years' imprisonment and a £2,000 fine, he was released in May 1896.

At the outbreak of the Anglo-Boer War (1899—1902) FitzPatrick helped to establish the Imperial Light Horse Regiment. Prevented by ill health from active service, he remained during the war in Britain as Official Adviser on South African Affairs to the British Government. Percy FitzPatrick was knighted in 1902 as a Knight Commander of the Order of Saint Michael and Saint George.

He served as one of eight Transvaal representatives in the national convention of 1908-9, where four British colonies were consolidated into the Union of South Africa. He went on to serve as a member of the parliament of the Union of South Africa, and successfully defended his Pretoria seat in 1906 and 1910. FitzPatrick and General J.B.M. Hertzog worked out the agreement that recognized English and Dutch as the official languages of the Union.

FitzPatrick kept wild animals that he brought back to Johannesburg after hunting trips at what now is Zoo Lake. Some of these animals formed the first stock of the Johannesburg Zoo. He also helped establish citrus farming in South Africa.

Sir James Percy FitzPatrick died in Amanzi, Uitenhage, Union of South Africa in 1931, aged 68, from undisclosed causes. He was buried at "The Look Out" , north of Uitenhage. The site offers a spectacular view of the Sunday's River Valley below.