Having been called to the Bar by Lincolns Inn he entered the diplomatic service.  After postings in Berlin, Munich (1831), Washington (1840), Turin (1849) and Madrid (1850) he was appointed secretary to the Legation at Mexico (1854) and became the Chargé daffaires.  
In the unreformed British diplomatic service there were no examinations; candidates were appointed by the influence of political friends.  This caused criticism.  In the House of Commons on 22 May 1855 the motion was
In this debate Lettsom was used as a case in point to illustrate the defects of the unreformed system.  It has been noted that Lettsom, "who had invariably conducted himself to the satisfaction of those who employed him", received one of the slowest promotions in the diplomatic service.  A diplomat was expected to be a gentleman and to have a private income whereby he could receive unpaid diplomatic appointments.  Hence nine of the twenty-three years of Lettsom's service were unsalaried; promotion was slow.  This glacial treatment did not apply, however, to those who had powerful political friends, for they were soon appointed to agreeable capitals at enormous salaries.   The motion was carried by 112 votes to 57,  Mr Otway MP remarking that "The person who had shown himself to be the fittest man, whether he was the son of a Peer or a tailor, should be chosen".
While in Mexico the British government suspended relations with that country on Lettsoms representation, and he was the object of an attempted assassination.  Between 1859 and 1869 Lettsom was appointed Consul-General and Chargé dAffaires to the Republic of Uruguay.