Malta's national poet, sometimes called “the bard of Malta,” or “the Chaucer of Malta.” His work has both romantic and classical affinities. His love of nature and his motherland together with his religious sensibility exemplify the former; his fondness for traditional metre (notably in his sonnets, which are considered particularly fine) exemplifies the latter.

Karm was ordained a priest at the age of 23 and worked as a seminary lecturer and diocesan grammar-school teacher until his dismissal by the ecclesiastical authorities in 1921. He then became assistant director of the National Library, retiring in 1936. He subsequently worked as lexicographer on the official English-Maltese dictionary. Karm was awarded a doctorate of letters by the Royal University of Malta in 1945, and in 1956 he was made a Commander of the Order of the British Empire.

He had already won distinction as a writer in Italian before being invited by the journal Il-Habib (“The Friend”), in 1912, to contribute verse in Maltese. Karm influenced several generations of Maltese writers and has been considered instrumental in paving the way for the adoption of Maltese as the official language of the island in 1934. He wrote the lyrics of the national anthem, Innu Malti (1923; “Hymn of Malta”). His works have been translated into English, French, Arabic, and Esperanto. Karm himself translated into Maltese the poem I Sepolcri (The Sepulchres) by the late 18th- and early 19th-century Italian poet Ugo Foscolo, adding a coda of his own.

Karm's home in Valletta, where he lived from 1910 to 1936, became a tourist attraction after World War II.