Mr Guthrie was now engaged by the earl of Loudon as tutor to his son lord Mauchlin. In that situation he remained till his ordination as first minister of Fenwick—a parish which had till that time formed part of that of Kilmarnock. Lord Boyd, the superior of the latter, a staunch royalist and a supporter of the association formed at Cumbernauld in favour of the king in 1641,—had also the patronage of Fenwick. This nobleman was most decidedly averse to Mr Guthrie’s appointment—from what reasons does not appear, although we may be allowed to conjecture that it arose either from Mr Guthrie’s decided principles, or from the steady attachment of the Loudon family to the presbyterian interest. Some of the parishioners, however, had heard him preach a preparation sermon in the church of Galston, became his warmest advocates, and were supported in their solicitations by the influence of the heritors. Mr Guthrie was after some delay ordained minister of the parish on the 7th of November, 1644.

The difficulties which Mr Guthrie had to encounter when he entered upon his charge were neither few nor unimportant. From the former large extent of the parish of Kilmarnock, the nature of the country, and the badness, in many cases the total want, of roads, a large mass of the people must have entirely wanted the benefits of religious instruction. He left no plan untried to improve their condition in that respect. By every means in his power he allured the ignorant or the vicious: to some he even gave bribes to attend the church; others in more remote districts he visited as if incidentally travelling through their country, or even sometimes in the disguise of a sportsman; in such cases, says the author of the Scots Worthies, "he gained some to a religious life whom he could have had little influence upon in a minister’s dress."

In August, 1645, Mr Guthiie married Agnes, daughter of David Campbell of Skeldon in Ayrshire, but he was soon called to leave his happy home by his appointment as a chaplain to the army. He continued with them till the battle of Dunbar was fought and lost: after it he retired with the troops to Stirling from thence he went to Edinburgh, where we find him dating his letters about six weeks afterwards. The last remove was viewed by the clergy with considerable jealousy; and their suspicions of an "intended compliance," intimated to him in a letter from Mr Samuel Rutherford, must have been a source of much distress and embarrassment to him. That such was not his intention his subsequent conduct showed, nor was it any part of Cromwell’s policy to convert the Scottish clergy by torture or imprisonment. Upon entering the metropolis he intimated that he did not wish to interfere with the religion of the country and that those ministers who had taken refuge in the castle might resume their functions in their respective parishes.

But while Cromwell determined to leave the clergy and people of Scotland to their own free will in matters of religion, it is lamentable to observe the they split into factions, which were the cause of some violent and unchristian exhibitions. When they divided into the grand parties of resolutioners and remonstraters, or protesters, Mr Guthrie joined the latter: but he displayed little of that animosity which so unfortunately distinguished many of his brethren. He preached with those whose political opinions differed from his own, and earnestly engaged in every measure which might restore the peace of the church. But while we cannot but lament their existence, these dissensions do not seem to have been unfavourable to the growth of religion in the country. On the contrary, both Law and Kirkton inform us that "there was great good done by the preaching of the gospel" during that period, "more than was observed to have been for twenty or thirty years." We have some notices of public disputes which took place during the Protectorate,—particularly of one at Cupar in 1652, between a regimental chaplain and a presbyterian clergyman. [Lamont’s Diary, ed. 1830, p. 48.] It is highly probable that this freedom of debate, and the consequent liberty of professing any religious sentiments, may have been one great cause of so remarkable a revival.

From this period to the Restoration, few interesting events present themselves to the reader of Scottish history. We do not find any notice of Mr Guthrie till the year 1661, when all the fabric which the presbyterians had raised during the reign of Charles I. was destroyed at one blow. Of the exaggerated benefits anticipated from the restoration of his son every one who has read our national history is aware. Charles II. was permitted to return to the throne with no farther guarantee for the civil and religious liberties of his people than fine speeches or fair promises. It was not long before our Scottish ancestors discovered their mistake; but the fatal power, which recalls to the mind the ancient fable of the countryman and the serpent, was now fully armed, and was as uncompromising as inhuman in its exercise. In the dark and awful struggle which followed, Mr Guthrie was not an idle spectator. He attended the meeting of the Synod of Glasgow and Ayr, which was held at the former place in April, 1661, and framed an address to the parliament at once spirited and moderate. Unfortunately, when this address was brought forward for the approbation of the Synod, the members were so much divided that one party declared their determination to dissent in the event of its being presented. In such circumstances it could only prove a disgraceful memorial of their distractions, and many, otherwise approving of its spirit and temper, voted against any further procedure. The "Glasgow Act," by which all ministers who had been ordained after 1649, and did not receive collation from their bishop, were banished soon followed; but it did not affect Mr Guthrie.

Through the good offices of the earl of Glencairn, (to whom Mr Guthrie had some opportunity of doing a favour during his imprisonment before the Restoration,) he had hitherto escaped many of the evils which had visited so large a majority of his brethren. Dr Alexander Burnet, archbishop of Glasgow, now began to act with great severity towards the nonconforming clergy of his diocese. To the intreaty of lord Glencairn and of other noblemen, that he would in the meantime overlook Mr Guthrie, the haughty prelate only replied "That cannot be done,—it shall not: he is a ringleader and a keeper up of schism in my diocese." With much difficulty he prevailed upon the curate of Calder, for the paltry bribe of five pounds, to intimate his suspension. The parishioners of Fenwick had determined to oppose such an intimation even at the risk of rebellion, but were prevailed upon to desist from an attempt which would have drawn undoubted ruin upon themselves. The paltry curate, therefore, proceeded upon his errand with a party of twelve soldiers, and intimated to Mr Guthrie, and afterwards in the parish church, his commission from archbishop Burnet to suspend him. Wodrow mentions that when he wrote his history it was still confidently asserted "that Mr Guthrie, at parting, did signify to the curate that he apprehended some evident mark of the Lord’s displeasure was abiding him for what he was now doing,"—but that this report rested on very doubtful authority. "Whatever be in this," he continues, "I am well assured the curate never preached more after he left Fenwick. He came to Glasgow, and whether he reached Calder—but four miles beyond it—I know not: but in four days he died in great torment of an iliac passion, and his wife and children died all in a year or thereby. So hazardous a thing is it to meddle with Christ’s sent servants."

Mr Guthrie remained in the parish of Fenwick for a year after this time without preaching. In the autumn of 1665, he went to Pitforthy, where his brother’s affairs required his presence. He had only been there a few days when a complaint which had preyed upon his constitution for many years, a threatening of stone, returned with great violence, accompanied by internal ulceration. After some days of extreme pain, in the intervals of which he often cheered his friends by his prospects of happiness in a sinless state, he died in the house of his brother-in-law, the Rev. Lewis Skinner, at Brechin on the 10th of October, 1665.

Mr Guthrie would in all probability never have appeared before the world as an author, had it not been requisite in his own defence. In 1656 or 1657, a volume was published, containing imperfect notes of sermons preached by him on the 55th chapter of Isaiah. Although it had a considerable circulation, he was not less displeased with its contents than the pomposity of its title. It was true, indeed, that it was not brought forward as his production, yet Mr Guthrie "was reputed the author through the whole country," and therefore bound to disclaim it in his own vindication. He accordingly revised the notes which he had preserved of these sermons; and from thence wrote his only genuine work "The Christian’s Great Interest," now better known by the title of the First Part, "The Trial of a Saving Interest in Christ." Any praise that could here be bestowed upon the work would be superfluous. It has gained for itself the best proof of its merits,—a circulation almost unparalleled among that class of readers for which it was perhaps chiefly intended, the intelligent Scottish peasantry.

John Howie mentions, in his Scots Worthies, that "there were also some discourses of Mr Guthrie’s in manuscript," out of which he transcribed seventeen sermons, published in the year 1779. At the same period there were also a great number of MS. sermons and notes bearing his name. Some of these had apparently been taken from his widow by a party of soldiers who entered her house by violence, and took her son-in-law prisoner in 1682.

It may be necessary here to allude to another work connected with Mr Guthrie’s name, - "The heads of some sermons preached at Fenwick in August, 1662, by Mr William Guthrie, upon Matt. xiv. 24, &c. anent the trials of the Lord’s people, their support in, and deliverance from them by Jesus Christ," published in 1680, and reprinted in 1714. This work was wholly unauthorized by his representatives, being taken, not from his own MSS. but from imperfect notes or recollections of some of his hearers. His widow published an advertisement disclaiming it, a copy of which is preserved in the Advocates’ Library, among the collections of the indefatigable Wodrow.