Thomas Lowndes began practicing law in Charleston after admission to the bar in 1789. He entered South Carolina's House of Representatives in 1792 and remained through 1799, representing the urban parishes of St Philip and St Michael. His family was already prominent in state politics, but his own service belonged to the Federalist party. He then moved from the state legislature to the federal House of Representatives.

Lowndes represented South Carolina's first district in the Seventh and Eighth Congresses, from March 1801 to March 1805. His district included Charleston and neighboring parishes. The 1803 election returns show the close contest that returned him: he received 422 votes to Republican Robert Marion's 385. His strongest recorded support came from Charleston, while several outlying parishes favored Marion. The result placed a Federalist representative in a Congress increasingly dominated by Jeffersonian Republicans.

His congressional service ended in 1805, and an attempt to return in 1808 failed. He then withdrew from public office and devoted himself to managing his estate, living both at Oaklands plantation and in Charleston. He remained retired until his death in 1843. He combined legal practice, state legislation and two terms in Congress before a long retirement on his plantation. He should be distinguished from his younger half-brother William Lowndes, whose later congressional leadership and national reputation arose from a separate political career.