Henderson, however, chose more wisely, for his favourite by-study was that of astronomy, which he commenced so early as during the period of his apprenticeship—which he prosecuted so as not to retard his professional pursuits—and to which he did not wholly resign himself, until he found that he could do it with safety and advantage. In Dundee he applied to astronomical investigations during the leisure hours of his apprenticeship, and continued in like manner to prosecute them after his arrival in Edinburgh, where his proficiency in the science gradually introduced him to the acquaintanceship of Professors Leslie and Wallace, Captain Basil Hall, and other distinguished scientific men of the northern capital. At this time it was fortunate for him that an observatory had been erected upon the Calton Hill, which, though poorly furnished with the necessary apparatus, had yet enough to satisfy the wants of ordinary inquirers. Of this establishment Professor Wallace had charge; and finding that he could intrust Mr. Henderson, though a stranger, with free access and full use of the instruments, the latter gladly availed himself of the opportunity, by which he improved himself largely in the practical departments of astronomical science, in addition to the theoretical and historical knowledge of it which he had already acquired. These studies upon the Calton Hill were the more commendable, when we take into account his weak health, his tendency to a disorder in his eyes, and his diligence in the duties of his laborious profession, which he had too much wisdom and self-denial to neglect.

It was not till 1824 that Mr. Henderson presented himself to notice as an astronomer, which he did by communicating with Dr. Thomas Young, at that time superintending the "Nautical Almanac." To him he imparted his method of computing an observed occultation of a fixed star by the moon, which Young published as an improvement upon his own, in the "Nautical Almanac" for 1827, and the four following years, to which Henderson added a recent method and several calculations. These methods were also announced to the scientific world by being published in the "London Quarterly Journal of Science," while Mr. Henderson received for them the thanks of the Board of Longitude. In 1827 he communicated a paper to the Royal Society of London, "On the Difference of Meridians of the Royal Observatories of London and Paris," which the society published in its "Transactions." Mr. Henderson’s reputation, as a scientific and practical astronomer, was now established, while his communications to Dr. Young were about to change his public career in life for one more congenial to his favourite pursuits. The latter, who held the important office of secretary to the Board of Longitude, died, and after this event a memorandum was found in his hand-writing, which he had deposited with Professor Rigaud, desiring that, on the event of his death, the Admiralty should be informed that no one was so competent, in his opinion, to succeed him as Mr. Henderson. The Admiralty were pleased to think otherwise, and appointed Mr. Pond, the Astronomer-Royal, to the charge. Soon after another important vacancy occurred by the death of Mr. Fallows, who had charge of the observatory at the Cape of Good Hope; and on the Admiralty offering it to Mr. Henderson, he closed with the proposal, and repaired to the Cape in 1832, although it was to sojourn among strangers, and with a disease of the heart, which, he knew, might at any time prove fatal. His scientific exertions during his short residence at the Cape of Good Hope, attested his self-devoted zeal in behalf of astronomy; for, independently of his official duties, the mass of observations and calculations which he had stored up, would have sufficed for the lifetime of a less earnest astronomer. Such incessant labour proved too much for his constitution, and in little more than a year he was obliged to return home, where, fixing his residence in Edinburgh, he devoted himself to the task of arranging the large mass of valuable materials which he had collected at the Cape. While he was thus employed, an agreement was entered into, in 1834, between the government and the Astronomical Institution of Edinburgh, by which the Institution agreed to give up the use of their observatory on the Calton Hill to the University, while the government engaged to convert it into a public institution, furnish it with suitable instruments, and provide for an observer and assistant. This movement made it necessary to fill up the professorship of practical astronomy, which had been vacant sixteen years; and on Lord Melbourne applying to the Astronomical Society of London for advice upon the subject, Mr. Henderson was recommended to the chair, to which he was appointed, with the honorary office of Astronomer-Royal for Scotland, being the first that had held it. Having thus obtained a situation that realized the beau ideal of his ambition for scientific distinction, opportunities of study, and means of comfort, he, in 1836, married Miss Adie, eldest daughter of Mr. Adie, the talented inventor of the sympiesometer.