The story deals with Métis rebel leader Louis Riel's antagonistic relationship with the newly established Canadian government.

The book explores Riel's possible schizophrenia—he believed God had named him Prophet of the New World, destined to lead the Métis people to freedom.

The work is noted for its emotional disengagement, its intentionally flat dialogue, and a minimalist drawing style inspired by that of Harold Gray's comic strip Little Orphan Annie.

The lengthy, hand-lettered appendix provides insight into Brown's creative process and biases and highlights where he changed historical facts to create a more engaging story, such as incorporating a conspiracy theory not widely accepted by historians.

[3] The story comprises 241 pages of the 271-page book, and is supplemented with a complete scholarly apparatus: a foreword, bibliography, index, map section and extensive end notes.

[8] Many of Brown's favourite topics are entwined in Louis Riel: anti-authoritarianism, outsider religion, insanity, and accuracy and objectivity in nonfiction.

In 1995, Brown published the anti-psychiatry comics essay "My Mom was a Schizophrenic", in which he examines society's role in mental illness, and questions the medical profession's accepted beliefs about it.

[17] He also came across books by researcher Don McLean and historian Douglas N. Sprague that advanced the conspiracy theory that the 1885 North-West Rebellion was deliberately provoked by Prime Minister John A. Macdonald to gain support for the building of the transcontinental railway.

[25] The government of the new Dominion of Canada (established 1867), under Prime Minister John A. Macdonald, has made a deal with the Hudson's Bay Company to purchase Rupert's Land—vast tracts of land in northern North America.

In the Red River settlement, the Métis, led by Louis Riel, dodge political manoeuverings on the part of Lieutenant Governor William McDougall and some of the English-speaking settlers, while seizing Fort Garry.

After an armed standoff at English-speaking settler John Schultz's home, the Métis declare a provisional government and vote Riel their president, with an even number of French and English representatives.

During his exile, he has a visionary experience on a hilltop in Washington, D.C., in which God names him David, the Prophet of the New World,[26] and tells him to lead the Métis to freedom.

Finally, after being ignored for too long, the Métis search for Riel in Montana, in the hope that his return will force the Canadians to take their claims seriously.

In the hopes that he will get money from the Canadian government for his tenure administering the Red River settlement (by this time known as Winnipeg), he moves his family to Batoche (now in Saskatchewan) in mid-1884.

[37] Brown depicts the Prime Minister in the role of scheming villain and caricatures his features in an absurd manner, giving him an extremely oversized nose[38] and showing him as a drunk.

Brown takes a distanced approach and relies faithfully on his source material—he focuses on the concrete and corporeal and eschews techniques of speculation such as thought balloons.

[12] The book makes frequent deliberate use of silent panels, focused on imagery[43] with the narrative moved forward by the characters' actions.

[26] Printed on yellowish paper,[45] each page conforms strictly to a rhythmic six-panel grid,[46] in contrast to the free placement of panels that characterized Brown's autobiographical period.

[47] Tone and mood are set by the composition of the panels, as during Riel's trial when all tonal variation is dropped, and the white figures are placed against a heavy black background,[32] which emphasizes the claustrophobic atmosphere.

[9] He frequently cited Harold Gray of Little Orphan Annie as the primary influence on the drawing style of Louis Riel—restrained artwork which avoids extreme closeups,[48] and blank-eyed characters with large bodies, small heads, and oversized noses.

[50] Brown also acknowledges significant debts to Jack Jackson's historical comics,[51] Hergé's The Adventures of Tintin,[52] and the extremely exaggerated style of Larry Gonick's Cartoon History of the Universe.

[54] When he began Louis Riel, Brown had increasingly been making use of notes and appendices in his work,[55] beginning with his researching and annotating the 1994 comics essay, "My Mom was a Schizophrenic".

[57] Alan Moore's use of extensive end notes in his and Eddie Campbell's From Hell, another fictional reconstruction of a historical event, influenced Brown's appendices.

[34] In the comics essay "Dance of the Gull Catchers" which closes the From Hell appendices, Moore metaphorically reveals to the reader the myriad choices he could have made from the available historical evidence when putting together his version of the Jack the Ripper story.

[59] Brown makes explicit the inaccuracies in the book,[60] as when he realized his drawings of William McDougall did not match up with descriptions of him by biographers as a "portly" and "heavily built man".

[61] He also admits that he deliberately changed some of the historical details, as when he has Prime Minister Macdonald in talks with the Hudson's Bay Company in London—Macdonald was not in London at that time and did not directly participate in the negotiations.

In other instances, Brown noted where he paid special care to historical details: the dialogue of Riel's trial comes directly from court transcripts.

[62] Brown makes clear in his notes the amount of research undertaken for the book, emphasizing both its authenticity and his desire to show the different aspects of Riel's ambiguous story.

The characters' heads became smaller while their bodies and hands grew larger, with Riel appearing "like the Hulk in a wool suit" after his hilltop religious revelation.

[85] It is regularly cited as being at the forefront of a trend in historical graphic novels, along with Art Spiegelman's Maus and Marjane Satrapi's Persepolis.