Walker was a protégé of the chemist William Cullen and a colleague of Dugald Stewart, Joseph Black and several other Edinburgh professors who shaped the intellectual milieu of the Scottish Enlightenment.

During his long career, he became a distinguished botanist, chemist, geologist, hydrologist, meteorologist, mineralogist, zoologist and economic historian, as well as being a minister in the Church of Scotland.

He was licensed to preach by the Presbytery of Kirkcudbright in 1754 but was not ordained into the Church of Scotland until 1758, initially being minister of Glencorse just south of Edinburgh, moving to Moffat in 1762 and to Lochmaben.

During the 1750s he continued to pursue scientific subjects by studying chemistry under Professor William Cullen and by joining Edinburgh's Philosophical Society.

These tours allowed him to make religious and ethnographic observations for the church and to take scientifically oriented notes on northern Scotland's minerals, plants, animals, and climate.

He gives a good description both of the symptoms (with "exquisite pain [in] the interior parts of the limbs") and of the tick vector itself, which he describes as a "worm" with a body which is "of a reddish colour and of a compressed shape with a row of feet on each side" that "penetrates the skin".

[3] It was also during this period that he collected samples of the mineral which came to be known as strontianite from its type locality, thus setting in process the identification and analysis of the new alkaline earth Strontium.

By the mid part of the decade, it became clear that Robert Ramsay, the University of Edinburgh's ailing Professor of Natural History, would soon need to be replaced.

As shown by Matthew Daniel Eddy,[4] Walker developed a sophisticated theory of the earth based on evidence gathered from geochemistry and human history.

Sometime in the late 1790s he began to lose his sight and several of his lectures were taken over by Dr Robert Jameson, a physician and former student who had also studied in mainland Europe.