Charles Metcalfe was second son of Thomas Theophilus Metcalfe, then a major in the Bengal Army. The father afterwards became a director of the East India Company and was created a baronet on 21st December 1802. Metcalfe's mother was Susannah Selina Sophia, widow of Major John Smith of the East Indian Army, and daughter of John Debonnaire of the Cape of Good Hope. At an early age, Charles was sent to a preparatory school at Bromley in Middlesex and, in January 1796, went to Eton, where he showed remarkable powers of application and a great distaste for all athletic sports. Leaving Eton on 1st April 1800, he was appointed to a Bengal writer-ship on 13th October and, in January 1801, arrived at Calcutta. He was the first student admitted to Lord Wellesley's College of Fort William, where he studied oriental languages with some success. On 3rd December 1801, he was nominated assistant to the embassy to the Arab States, an appointment which was cancelled a few days afterwards at his own request for that of assistant to the resident with Dowlut Rao Scindiah. Metcalfe's connection with Scindiah's Court was, however, brief as he soon found that he was unable to agree with Colonel Collins, the resident. On 4th October 1802, Metcalfe became an assistant in the Chief Secretary's Office at Calcutta and was transferred, on 4th April 1803, to a similar position in the Governor-General's Office. In the Summer of 1804, Metcalfe was attached to the headquarters of Lake's Army, in the capacity of Political Assistant and, as a volunteer, took part in the storming of the Fortress of Deeg (24th December 1804). He acted, successively, as Political Agent to General Smith and General Dowdeswell and, on 10th January 1806, was received in full durbar by Holkar, with whom a treaty had been concluded a few days previously. Metcalfe was appointed First Assistant to the Resident at Delhi on 15th August 1806 and, in August 1808, was despatched on a special mission to Lahore. After a series of tedious negotiations, Metcalfe obtained all that he had demanded of Runjeet Singh, who withdrew his troops to his own side of the Sutlej and concluded a treaty of general amity with the British Government at Vmritsur on 25th April 1809. By the adroitness with which he overcame the many difficulties of this mission, Metcalfe won, for himself, a considerable reputation as a diplomatist at the age of twenty-four.

From August 1809 to May 1810, Metcalfe acted as Lord Minto's Deputy Secretary during the Governor-General's visit to Madras and, on 15th May 1810, was appointed Acting Resident to the Court of Dowlut Rao Scindiah. On 25th February 1811, he was promoted to the post of Resident at Delhi. By his careful administration, the industrial resources of the territory were largely developed, while his scheme for the settlement of Central India largely influenced the policy of the Governor-General, Lord Moira (afterwards the Marquis of Hastings). In 1816, he refused the post of Financial Secretary and, on 29th January 1819, became secretary in the secret and political department and Private Secretary to the Governor-General. Accustomed to an independent command, Metcalfe quickly found his new situation irksome and, on 26th December 1820, was appointed resident at Hyderabad. An attempt made by him to remove the baneful influence of the money-lending firm of William Palmer & Co., which was overshadowing the Nizam's Government, brought upon Metcalfe the displeasure of the Governor-General, who rejected his scheme for opening a six per cent loan, guaranteed by the British Government, by which the Nizam's huge obligations to Palmer's house and other creditors might be paid off. Soon after Hastings's return to England, where these pecuniary transactions were warmly discussed in the Court of Proprietors during a six days' debate, the debt due to William Palmer & Co. was discharged and, in less than a year, the house became bankrupt.

On the death of his elder brother, Theophilus John, in August 1822, Metcalfe succeeded to the baronetcy. In the following year, he was invalided and went to Calcutta, but returned to Hyderabad in 1824. On 26th August 1825, he was appointed Resident and Civil Commissioner in Delhi Territories, and Agent to the Governor-General for the affairs of Rajpootana. Under his advice, the Government supported the claims of Bulwunt Singh against the usurpation of his uncle Doorjun Saul and, in January 1826, Bhurtpore was successfully stormed by Lord Combermere and Doorjun Saul taken prisoner. On 24th August 1827, Metcalfe became a member of the Supreme Council which, at that time, consisted of the Governor-General, the Commander-in-Chief and two members of the Civil Service. By a resolution of the Court of Directors, on 14th December 1831, Metcalfe's period of service on the Council was extended from five to seven years. He was appointed to the newly created Government of Agra, on 20th November 1833, but owing to the absence from Bengal of the Governor-General (Lord William Bentinck), he was compelled to stay in Calcutta for some time as Vice-President of the Council and Deputy-Governor of Bengal. In December 1834, Metcalfe set out for the seat of his Government at Allahabad, but no sooner had he got there than he had to return to Calcutta in consequence of Lord William Bentinck's resignation. By virtue of a resolution of the Court of Directors in December 1833, Metcalfe acted as Provisional Governor-General during the interval between the departure of Lord William Bentinck and the arrival of Lord Auckland (20th March 1835 to 4th March 1836). The directors wished that Metcalfe should remain in office, but the Whig Ministry refused to sanction the appointment on the ground that it was not advisable to appoint any servant of the company to the highest office of the Indian Government. Before Lord Melbourne had appointed a successor to Lord William Bentinck, there was a ministerial crisis and Lord Heytesbury was nominated by Sir Robert Peel. But before Lord Heytesbury set out, another ministerial crisis occurred: the tory appointment was cancelled and Lord Auckland was appointed. Metcalfe's short administration is chiefly distinguished by the act of 15th September 1835, which removed the vexatious restrictions on the liberty of the Indian press.

Shortly after the arrival of the new Governor-General, Metcalfe was invested with the Grand Cross of the Bath (14th March 1836). In the same month, the Agra Government having been meanwhile abolished, he was appointed Lieutenant-Governor of the North-Western Provinces, the headquarters of which were fixed at Agra instead of Allahabad. In filling up the vacant Governorship of Madras, Metcalfe was passed over by the directors, who had been greatly displeased by his giving legal sanction to the liberty of the press. In consequence of this slight, Metcalfe resigned his Lieutenant-Governorship on 1st January 1838 and retired from the service. He reached England in May 1838 and took up his abode at Fernhill Park, near Windsor (Berkshire). While making arrangements for contesting Glasgow in the radical interest, Metcalfe was appointed Governor of Jamaica (11th July 1839). He was admitted as a member of the Privy Council on 31st July and, on 26th September following, was sworn in as Governor at Spanish Town. By his conciliatory conduct, he speedily effected the reconciliation of the colony to the mother-country and brought about a better feeling between the proprietors and the emancipated black people. Having accomplished what he had been sent out to do, Metcalfe resigned his office and returned to England on 2nd July 1842. In January 1843, he accepted the Government of Canada and, on 30th March following, took the oaths at Kingston as Governor-General. Owing to the burning question of responsible government and the inflamed state of party spirit in the colony, Metcalfe's position was one of extreme difficulty. His attempts to conciliate all parties displeased the executive council, who were determined to reduce the Governor-General to a mere passive instrument in their hands, and were supported in their endeavours by the majority of the representative assembly. In consequence of Metcalfe's refusal to admit their right to be consulted about official appointments, all the members of the council, with one exception, resigned in November 1843. For some time, he was therefore without a full council, but after the general election in November 1844, which resulted in a slight majority for the Government, he was able to fill up all the vacant places with men of moderate views. Meanwhile, Metcalfe had for a long time been suffering from a malignant growth on his cheek which, at length, deprived him of the sight in one eye. Unwilling to leave the Government to his successor in a state of embarrassment, he still struggled on at his post. As a 'mark of the Queen's entire approbation and favour' he was created Baron Metcalfe of Fernhill in the county of Berkshire on 25th January 1845. Before the year was out, he had become physically unfit for work and, having resigned his post, he returned to England in December 1845 in a dying state. After patiently enduring still further agony, he died at Malshanger, near Basingstoke in Hampshire, on 5th September 1846. He was buried in the family vault in the parish church of Winkfield, near Fernhill, where there is a tablet to his memory. The inscription was written by Lord Macaulay.

Metcalfe was an able and sagacious administrator, of unimpeachable integrity and untiring industry. His self-reliance and imperturbable good humour were alike remarkable, though perhaps his undeviating straightforwardness was his most marked characteristic. Metcalfe did not take his seat in the House of Lords. As he never married, the Barony became extinct upon his death, while the baronetcy devolved upon his younger brother, Thomas Theophilus Metcalfe. A selection of Metcalfe's early papers, Indian council minutes and colonial despatches has been edited by Sir J. W. Kaye (London, 1855). Two of Metcalfe's speeches delivered in the Jamaica legislature have been separately published (London, 1840). Metcalfe is said to have published, in 1838, a pamphlet on the payment of the national debt, as well as an anonymous pamphlet entitled 'Friendly Advice to the Conservatives'. His essay 'On the best Means of acquiring a knowledge of the Manners and Customs of the Natives of India' is printed in the first volume of 'Essays by the Students of the College of Fort William in Bengal' (Calcutta, 1802).