He surveyed southern India, making use of local interpreters and scholars to study religion, oral histories, inscriptions and other evidence, initially out of personal interest, and later as a surveyor.

His collections consisting of thousands of manuscripts, inscriptions, translations, coins and paintings, which were acquired after his death by the India Office Library and are an important source for the study of Indian history.

Little is known of his early life but he is thought to have started his work as a Comptroller of the Customs at Stornoway from 1778 to 1783, possibly through the influence of his father's association with the Mackenzie Earls of Seaforth.

When Lord Napier died in 1773, Kenneth Mackenzie helped Colin to obtain commission with the British East India Company to join the Madras Army.

Hester introduced Mackenzie to some Brahmins to obtain information on Hindu mathematical traditions as part of the biographical memoir on John Napier and the history of logarithms.

After the defeat of Tipu, he led the Mysore survey between 1799 and 1810 and one of the aims was to establish the boundaries of the state as well as the territories ceded by the Nizam.

When he began the survey, he was concerned that he had no linguistic skills and was more appalled by the lack of British competence in south Indian languages.

[9] Mackenzie was told that his survey was not to be "mere military or geographical information, but that your enquiries are to be extended to a statistical account of the whole country."

He wrote to Barry Close that he would not "descend to the minutiae" of measuring cultivated and uncultivated land but would instead focus on that which was of political and military importance.

One of his chief interpreters was a man named Kavelli Venkata Boria (IAST kāvelī veṃkeṭā boraiyāḥ, there are variations in spelling) who Mackenzie first met in 1796, shortly after his return from Ceylon.

[12] Stating the aims of his survey, he wrote from the perspective of a historian in a letter to Major Merwick Shawe in 1805:[13] The elucidation of the History of the several Governments that have rapidly succeeded in this Stage will I conceived be very interesting, as by the Inscriptions, Grants & other Documents that came into my hands, a regular Progress is traced up to the first Mahomedan invasion in the 13th Century & even beyond it to the 8th but more obscurely; & in several instances still further, these consist not merely of a dry Chain of uninteresting facts but are connected by various illustrations of the genious & manner of the People, their Several Systems of Government & of Religion, & of the predominant causes that influence their Sentiments & opinions to this day; lights are derived on the Tenures of lands, the origin & variety of the several classes, and the genius and Spirit of the Government prevalent generally in the South for centuries from Several Documents illustrating claims & pretension not foreign to modern discussions; ... confirming the utility of this undertaking to the existing Government from a knowledge of Institutions that influence so considerable a part of the Population of the Empire.Among Mackenzie's vast collection of illustrations is a set of 85 sketches made at Amaravati.

The second volume bore the title A Collection of Monuments, Images, Sculptures &c. illustrative of The Ancient History, Religion & Institutions of the Island of Java and of the Adjacent Isles: Taken under the immediate Inspection & Direction of Lieutenant Colonel Colin Mackenzie in the course of a Tour & of different Excursions through the Island of Java in the years 1811-1812 & 1813 and included numerous sketches and a few watercolours.

[16] In 1767, the East India Company under Lord Clive had appointed James Rennell as Surveyor General for Bengal.

[7] On 26 May 1815 he was appointed Surveyor General of India with his headquarters at Fort William in Calcutta but he was allowed to stay on in Madras to help reorganize the surveys.

He appointed Benjamin Swain Ward (1786–1835) to survey Travancore, Lieutenant Peter Eyre Conner (born 5 August 1789, died 29-April-1821 at Hyderabad) (Sometimes given only as Lt. Connor[18]) for Coorg (then written as Codugu or Koorg), Francis Mountford (1790–1824) to Guntur and James Garling (1784–1820) to the Nizam's territories.

[19] The government in an attempt to hasten his move to Calcutta sent the yacht, HC Phoenix to transport him and his family from Madras on 24 June 1816.

[4] Fulcher was a fellow traveller on the ship to England and her original plan was to move to Stornoway to live with Colin's sister.

James Prinsep declared that "..The qualifications of Cavelly Venkata for such an office, judging of them by his 'abstract,' or indeed of any native, could hardly be pronounced equal to such a task...".

[28][29] Lechmiah received a monthly pension of 300 rupees and was given a grant of a Shotrium (or Shrotrium[30]), land given as a reward for Civil officers.

[26][32] Studies of the maps made by Mackenzie's survey are considered to have the potential to highlight interesting archaeological sites as well as provide information on the organization and structure of poligar chiefdoms which were dismantled after British takeover.