After leaving school in 1910, MacDiarmid worked as a journalist for five years. He then served in the Royal Army Medical Corps during the First World War. After the war, he married and returned to journalism. His first book, Annals of the Five Senses (1923) was a mixture of prose and poetry in English, but he then turned to Scots for a series of books, culminating in what is probably his best known work, the book-length A Drunk Man Looks at the Thistle. This poem is widely regarded as one of the most important long poems in 20th century Scottish literature. After that, he published several books containing poems in both English and Scots.

In 1928, MacDiarmid helped found the National Party of Scotland. He was also a member of the Communist Party of Great Britain. During the 1930s, he was expelled from the former for being a communist and from the latter for being a nationalist. In 1956, MacDiarmid rejoined the Communist Party. In 1950, George Orwell compiled a list of suspected communist sympathisers for British intelligence. He included MacDiarmid in this list.

As Grieve, he stood in the 1950 election in the Glasgow Kelvingrove constituency, as the Scottish National Party candidate, coming last with 639 votes. He also stood against Alec Douglas-Home in Kinross and Western Perthshire for the Communist Party at the 1964 election, taking only 127 votes. MacDiarmid listed Anglophobia amongst his hobbies in his Who's Who entry.

As his interest in science and linguistics increased, MacDiarmid found himself turning more and more to English as a means of expression so that most of his later poetry is written in that language. His ambition was to live up to Rilke's dictum that 'the poet must know everything' and to write a poetry that contained all knowledge. As a result, many of the poems in Stony Limits (1934) and later volumes are a kind of found poetry reusing text from a range of sources. Just as he had used Jameson's dialect dictionary for his poems in 'synthetic Scots', so he used Chambers Twentieth Century Dictionary for poems such as 'On a Raised Beach'. Other poems, including 'On a Raised Beach' and 'Etika Preobrazhennavo Erosa' used extensive passages of prose.This practice, particularly in the poem 'Perfect', led to accusations of plagiarism from supporters of the Welsh poet Glyn Jones, to which MacDiarmid's response was 'The greater the plagiarism the greater the work of art.' The great achievement of this late poetry is to attempt on an epic scale to capture the idea of a world without God in which all the facts the poetry deals with are scientifically verifiable.

MacDiarmid wrote a number of non-fiction prose works, including Scottish Eccentrics and his autobiography Lucky Poet. He also did a number of translations from Scottish Gaelic, including Duncan Ban MacIntyre's Praise of Ben Dorain, which were well received by native speakers including Sorley MacLean.

MacDiarmid grew up in the Scottish town of Langholm in Dumfries and Galloway. The town is home to a monument in his honour made of cast iron which takes the form of a large open book depicting images from his writings.

MacDiarmid lived in Montrose for a time where he worked for the local newspaper the Montrose Review.

MacDiarmid also lived on the isle of Whalsay in Shetland, in Sodom (Sudheim)

Hugh MacDiarmid is commemorated in Makars' Court, outside The Writers' Museum, Lawnmarket, Edinburgh.

Selections for Makars' Court are made by The Writers' Museum, The Saltire Society and The Scottish Poetry Library.

Hugh MacDiarmid sat for sculptor Alan Thornhill and a bronze was acquired by the National Portrait Gallery. The terracotta original is held in the collection of the artist The correspondence file relating to the MacDiarmid bust is held in the archive of the Henry Moore Foundation's Henry Moore Institute in Leeds.