The original name of the Topelius family was the Finnish name Toppila which had been Latinized to Toppelius by the author's grand father's grand father and later changed to Topelius. Zacharias Topelius was born at Kuddnäs, near Nykarleby in Ostrobothnia, the son of a physician of the same name (Zacharias Topelius the Elder), who was distinguished as the earliest collector of Finnish folk-songs. As a child he heard his mother, Katarina Sofia Calamnius, sing the songs of the Finland-Swedish poet Franzén. At the age of eleven, he was sent to school in Uleåborg and boarded with relatives in the possession of a lending library, where he nurtured his fantasy with the reading of novels.
He came to Helsinki in 1831 and became a member of the circle of young nationalist men surrounding Johan Ludvig Runeberg, in whose home he stayed for some time. Topelius became a student at the Imperial University of Helsingfors in 1833, received his filosofie magister degree in 1840, the Licentiate degree in 1844 and was made a Doctor of Philosophy in 1847, having defended a dissertation titled De modo matrimonia jungendi apud fennos quondam vigente ("About the custom of marriage among the ancient Finns"). Besides history, his academic studies had for periods been devoted both to Theology and Medicine. He was secretary of Societas pro fauna et flora fennica 1842-1846, was employed by the university library 1846-1861, and taught History, Statistics and Swedish at the school Helsingfors lyceum during the same period.
Through the intervention of a friend, Fredrik Cygnæus, Topelius was named professor extraordinary of the History of Finland at the University in 1854. He was made first ordinary professor of Finnish, Russian and Nordic history in 1863, and exchanged this chair for the one in general history in 1876. He was rector of the university from 1875 until 1878, when he retired as Emeritus Professor and received the title of verkligt statsråd (Russian: действительный статский советник; literally "state councillor", a Russian honorary title).
Quite early in his career he began to distinguish himself as a lyric poet, with the three successive volumes of his Heather Blossoms (1845-1854). The earliest of his historical romances was The Duchess of Finland, published in 1850. He was also editor-in-chief of the Helsingfors Gazette from 1841 to 1860. In 1878, Topelius was allowed to withdraw from his professional duties, but this did not sever his connection with the university; it gave him, however, more leisure for his abundant and various literary enterprises. Of all the multifarious writings of Topelius, in prose and verse, that which has enjoyed the greatest popularity is his Tales of a Barber-Surgeon, episodes of historical fiction from the days of Gustavus II. Adolphus to those of Gustavus III., treated in the manner of Sir Walter Scott; the five volumes of this work appeared at intervals between 1853 and 1867. Topelius attempted the drama also, with most success in his tragedy of Regina van Emmeritz (1854). Topelius aimed, with eminent but perhaps pathetic success, at the cultivation of a strong passion of patriotism in Finland.
Together with the composer Friedrich Pacius he wrote the libretto (in the style of Romantic nationalism) to the first Finnish opera: Kung Karls jakt. Topelius initially thought of writing a trivial entertainment, but having heard extracts from the opera project at a concert in 1851, he realized that Pacius was writing a grand opera on the theme of salvation, following the early Romantic style of Carl Maria von Weber's Der Freischütz (1821) and Oberon (1826). Topelius wrote the libretto in Swedish (though it was translated later by others), but its subject is emphatically Finnish.
Many of his works employed esoterical allegories harking to ancient mysteries and perhaps rosicrucian and alchemical themes, but on the other hand some of his short works examined the effects of the strong industrialisation of Finnish society.