He was born in New York City, the son of Catherine Pintard and John Searle, but on coming of age moved to Madeira, where he engaged in business with his brother John for sixteen years. Between 1753 and 1759, he made several trips to America, more particularly Philadelphia. In 1762, he married Nancy Smith of Waterford, England. He relocated to Philadelphia in 1765, where he continued working as a merchant and an agent for his brother's firm, accumulating great wealth. He signed the 1765 Non-Importation Agreement, whereby merchants pledged not to buy goods from England, in protest of the Stamp Act. He was elected by Congress in 1776 a commissioner for a national lottery that partially funded the Revolutionary War from 1776 to 1778. He then represented Pennsylvania as a delegate to the Continental Congress in 1778. While serving as a delegate, Searle started a cane fight with Charles Thomson, the Secretary of the Congress, claiming that Thomson misquoted him in the official minutes; the altercation resulted in both men receiving slashes to the face. Searle was a close friend of both John Adams and Benjamin Franklin.