First brought over to Canada by his uncle, Robert Hamilton, Thomas Clarke (he later dropped the "e") became a merchant and land speculator in his own right. He was born in Dumfries in Scotland about 1770 and arrived in Niagara in about 1792 as an apprentice to his uncle. After four years, part of which was spent in Hamilton's Queenston store, he left Hamilton to set up his own business as a merchant in Queenston in partnership with Samuel Street Jr. Robert Hamilton arranged for Clarke and Street to share a portion of the portaging contracts along the new Portage Road on the west bank of the Niagara River.

In 1799, Street left the partnership and was replaced by Robert Nichol, a close contact of Hamilton and possibly another Hamilton relative from Dumfries. This partnership lasted for four years, at which time Clarke went on his own. By 1805, he had bought the Falls Mills on the Niagara River from John Burch, and two years later sold them to Samuel Street Jr.. In 1810, he turned over his business to his clerk, James Kerby, and Robert Grant. Having dropped the "e" from his name sometime before, he again went into partnership with Samuel Street Jr., this time in the milling business. Clark and Street started with the Falls Mills and later bought the Bridgewater Mills, between the Falls Mills and Chippawa.

Clark also got into land speculation. He bought the Six Nation Block 4 in 1806 and sold the southern part to Robert Addison two years later. In 1811, he bought Block 1 with his cousin, William Dickson and transferred his part of the block to Dickson in 1816.

In the War of 1812, Clark was Lt. Col. of the 2nd Lincoln Militia, seeing action at Queenston Heights and Frenchman's Creek. He was present at the surrender of the American forces at Beaver Dams and took part in the raids on Fort Schlosser and Black Rock. At Black Rock, he suffered a wound that led to his return to Scotland to recover. During the war, Clark and Street had lost their Bridgewater and Falls Mills, which were both burned by the Americans. Only the Falls Mills were rebuilt.

Clarke married the daughter of the surgeon to the Indian Department but never had children. His great wealth went to Thomas Clark Street, the son of his partner. TC Street went on to become Canada's first millionaire.