He was born as Luka Mušicki in Temerin on 27 January 1777. His early education was most carefully conducted by his parents, first he was sent to a Serbian grammar school in Temerin; a German school in Titel; gymnasia (high schools) in Novi Sad and Segedin; and finally took up studying philosophy and law at the University of Pest, though aesthetics and poetry were always his favourite subjects. Edmund Burke, Johann Ludwig Schedius (1787–1847), Győrgy Alajos Szerdahelyi (1740–1808), and German poets Karl Wilhelm Ramler and Friedrich Gottlieb Klopstock made a big impact on him. He was also learning Greek and English. On leaving school with little means of support, he devoted himself to letters, and in 1800 published a collection of poems in Serbian magazines and journals. With Georgije Magarašević and Pavel Jozef Šafárik he published the Serpski Letopis. The poems encountered some adverse criticism from the Serbian ecclesiastical hierarchy, but secured for their poet the approbation and friendship of Vuk Karadžić. Henceforward Mušicki's life was steadily devoted to literary production and criticism. Shortly afterwards he became one of the secretaries of Metropolitan Stefan Stratimirović at Sremski Karlovci where he was subjected to a rigorous ecclesiastic supervision. His superiors were suspicious of his translating ancient Latin-speaking poets, like Horace, Lucian, Virgil and Ovid, whenever he had free time, but even more so when they found out that he knew Horace's De arte poetica by heart. Here his intentions of entering upon an academic career was for a time thwarted by his collision with his superiors. In 1802, after he had taken monastic vows and a new name ("Lukijan"), he was permitted to establish himself as privatdozent, lecturing at the Theological Seminary in Karlovci. Mušicki wrote extensively on aesthetic subjects, and poetry, and as a critic he had considerable influence, but only outside of the monastic community. It was not until 1812, however, that he attained the rank of archimandrite at the Šišatovac Monastery.
In 1828, at the age of 51, he was finally elevated from archimandrite to bishop of the Diocese of Upper Karlovci where he spent the remainder of his life. He died in Sremski Karlovci on 15 March 1837, at the age of sixty. Mušicki is principally remembered for his classical poetry and the many translations from the Latin of Horace. Most of his prose, in substance if not in manner, is that of a literary journalist. His lyrics, however, rank high in the context of Serbian 18th century literature, in pseudo-classicism. As a poet he was imitative: reminiscences of Dositej and Vezilić are noticeable in his patriotic songs; of Goldoni in his lyrical poems. He wrote hastily to satisfy artistic canons; but despite his faults he also had the merits of a pioneer, and in Serbia, Bosnia, Montenegro and other parts where Serbs live his name will endure. His collected poems and writings first appeared under the title Lukijana Mušickog stihodvorenia (The Works of Lukijan Mušicki) posthumously in Budapest in 1838 and 1840 (in two volumes), and the other two volumes were released in Novi Sad in 1844 and 1847. Born in Temerin, he became a monk, and later abbot of a monastery in Fruška Gora, whose religious poetry in Church Slavonic, a language distant from the spoken koine, but the only literary language of his time, was recognised and valued by the Serbian Orthodox Church. His secular poetry in vernacular tongue was frowned upon, to the point that he was threatened with defrocking, unless he repented, which in the end he did and stopped writing in what will only be justified as a written language by Vuk Karadžić.
In the opinion of his contemporaries, Mušicki revived the glories of the 18th century period of pseudo-classicism, and scholars such as Pavel Jozef Šafárik called Mušicki "Prince of Serbian Poetry", Petar I Petrović-Njegoš referred to him as "a genius of our race," while Đura Daničić said Mušicki was "the father of contemporary Serbian literature;" this is friendly hyperbole. Jernej Kopitar hailed him as "the Serbian Horace". While such judgements are naturally somewhat exaggerated, there is no doubt that Mušicki takes a very high place among Serbian poets of his day.
Indeed, Lukijan Mušicki ranks, like some of his contemporaries, Jovan Muškatirović, Aleksije Vezilić, Emanuil Janković, Vićentije Rakić, Pavle Solarić, Atanasije Stojković among the authors who have both a historical and an intrinsic importance in Serbian literature and science (Janković and Stojković in particular). They represented for the 18th century the literature of their time, and kept alive, the torch handed on to them by their maister Dositej Obradović. What is known of Mušicki's life can be read in Jovan Skerlić's History of New Serbian Literature (Istorija nove srpske književnosti), published in Belgrade (Second Edition, 1921) on pages 138–143.