A figure in Franco-Belgian comics whose career began in the early 1990s, Trondheim is mostly known as the author of Les formidables aventures de Lapinot (translated to English as The Spiffy Adventures of McConey) and the co-creator of comic fantasy series Dungeon with Joann Sfar, as well as his autobiographical series Les petits riens (translated to English as Little Nothings).

He first created La Mouche ("The Fly") for the Japanese market, and then redrew a French version from scratch, after which the character was adapted as an animated cartoon.

Trondheim's greatest breakthrough after Lapinot is arguably Dungeon (in French, Donjon), an ambitious series which he created with Joann Sfar, and which has enjoyed a fair amount of popular success.

In 2004, after a long and intensive period during which he steadily released new books at a frantic pace, Lewis Trondheim announced he was more or less retiring from the world of comic strips, stating he did not want his passion to become a "job".

He did draw and write a few stories within the following year, including a book reflecting on his decision to slow down, though the releases occurred at a much slower pace.

The webcomic was presented as an autobiographical work, chronicling the daily life of a single 30-year-old graphic designer and aspiring cartoonist, living in Paris.

That same year, Trondheim began the autobiographical webcomic Les Petits Riens (Little Nothings), published on his personal website, in line with his earlier works Approximativement and Carnets de bord.

[9] Trondheim has written or drawn more than a hundred titles, spanning a large spectrum of genres; some of the most notable are: Two volumes of McConey have been published in English by Fantagraphics in editions close to the original.