In a strict sense, John Jay was the first person to fulfill the interim role of representing the United States abroad, carrying the title Secretary for Foreign Affairs from 1784 until 1790. However, the first person to actually be given the title of Secretary of State was Thomas Jefferson, who assumed the office at the invitation of newly elected president George Washington in 1791.
Jefferson, who had been serving as the Minister to France since 1784, believed strongly in the cause of the Revolution and took the side of the French in its ongoing wars with the monarchies of Europe, especially its chief rival, Great Britain. This stance of support for a former ally of the American Revolution put him at odds with the president, who favored a completely neutral position in their war with the British, and the pro-business team of Alexander Hamilton and John Jay, who wished to remain neutral while continuing to trade with Great Britain.
Along with a number of other issues, including his battle with Hamilton over the latter's desire to create a national bank and what he felt was the aristocratic, quasi-monarchical cast of the Washington administration, this would soon lead to Jefferson's departure from his cabinet post.