Born in Eglingham, Tristram attended Durham Grammar School and associated with John Hancock, who influenced him towards natural history. Tristram became an Anglican clergyman, and resided with his family at Castle Eden, from where he made frequent trips abroad to the Sahara and Palestine. His article in the first issue of Ibis accepted the Darwinina theory of evolution a month before the publication of The Origin of Species. It may be claimed that he was the first zoologist to apply the theory of natural selection to his work on birds. Meanwhile he was the co-founder of St Hild's College in 1858.
Tristram wrote The Great Sahara (1860) but his main interest was the flora and fauna of Palestine. He was the author of the first ornithological surveys of the region, including The Land of Israel (1865), Natural History of the Bible (1867), The Land of Moab (1873) and The Flora and Fauna of Palestine (1884). Tristram's Warbler and Tristram's Serin are named after him.

In 1891, Tristram visited Japan, where his daughter had been a missionary for some time. The results of his investigations were published in Rambles in Japan: The Land of the Rising Sun (1895). Tristram was optimistic about the prospects for Christian missionaries, but it is interesting how often he saw Japan in relation to his own world. The old Tokaido highway is compared to 'our own Great North Road'; Nagoya castle was 'the Alnwick Castle of Japan' and the hills above Kyoto likened to 'our own Pennine Range'.