He studied theology at the University of Christiania and was graduated in 1845.
In 1849 he became a lecturer at the University of Christiania, and in 1860 became a professor, first in systematic theology and Dogmatic theology and from 1875 in church history. In 1858 he established, together with Carl Paul Caspari, an annual publication entitled Theologisk Tidskrift for den evangelisk-lutherske Kirke i Norge which he edited until 1891. During revival which went across Norway during the 1850s, he reflected the pietistic and ecclesial tradition of Hans Nielsen Hauge.
In 1879, he was conferred an honorary doctorate by the University of Copenhagen.
Both Gisle Johnsons plass in the district of Grünerløkka in Oslo and Gisle Johnsons gate in Trondheim were named in his honor.
He was a member of the Royal Norwegian Society of Sciences and Letters from 1858.