In 1814 he was called to the pulpit of the Tron Church in Glasgow and there for four years he exercised a remarkable preaching ministry. It cost him a lot to leave Kilmany. In his farewell sermon he said: "You have taught me that to preach Christ is the only effective way of preaching morality and out of your humble cottages I have gathered a lesson which, in all its simplicity, I shall carry with me into a wider theatre."

On Thursday, November 23, 1815, he delivered the first of his Astronomical Discourses, the preaching of which literally closed down the coffee rooms and business section of the city as merchants, their clerks and apprentices, flocked to hear Chalmers. Ready for publication in 1817, six thousands copies of the discourses were sold in ten weeks; nine editions in one year; and for a whole year the sales of his first volume of sermons kept pace with those of Walter Scott's newly published Tales of my Landlord. In London, preaching the anniversary service of the London Missionary Society, Chalmers found the Surrey Chapel packed by 7 a.m. for a service due to begin at 11 a.m.

"All the world," wrote Wilberforce in his diary, "is wild about Chalmers." In another entry he wrote, "I am off early to hear Chalmers. I was surprised to see how greatly Canning was affected: at times he was melted to tears." The verdict of the future member of Parliament was, "The tartan beats us all."

In 1818, Chalmers became the first minister of the new parish of St. John's, a parish of some ten thousand of the poorest of the city's population, and here took place one of the greatest social experiments of the century: an attempt to demonstrate that by the application of the normal parochial system of the Church, the problem of poverty could be tackled.

By means of a system of visitation by deacons in districts, he provided for the needs of all the poor in his parish from the church collections. From the surplus of income over expenditure he erected and endowed parochial schools. In 1832 he left St. John's for the Chair of Moral Philosophy at St. Andrews, having, as Lord Roseberry expressed it, "warmed Glasgow and inspired its citizens with a new conception of social zeal and evangelical fervor."

His sermons were massive, closely-reasoned productions of a first-class brain, often taking two hours to deliver, and read closely from the manuscript in a voice with a strong Fife accent. J. G. Lockhart said of him: "I have never heard any preacher whose eloquence is capable of producing an effect so strong and irresistible."

Chalmers held his manuscript in his left hand and followed each word with the index finger on his right hand. But once he got started, all constraints and awkwardness disappeared. One hearer said: "His whole being seemed to rush into his preaching." Another said: "His eyes were afire with intelligence and rapture and zeal. In spite of the reading his personality broke through to the people."

One who regularly heard him said: "His extempore discourses delivered to working men on the outskirts of Glasgow were far more effective and more truly eloquent than the sermons which he delivered with so much applause in the Tron Church." His style was cumbrous and pedantic and his sentences sometimes ran to an inordinate length. He had great powers of abstraction so that he could compose his sermons in moments snatched from travel or amid the interruptions of a life of many engagements.