"[2] In 1835, Thompson was elected as an Anti-Jacksonian to the 24th United States Congress to fill the vacancy caused by the death of Warren R. Davis.

In 1842 President John Tyler appointed Thompson Envoy Extraordinary and Minister Plenipotentiary to Mexico, where he served from February 10, 1842, to March 9, 1844.

After his wife died in 1848, he married Cornelia Jones of Wilmington, North Carolina, and eventually moved to Paris Mountain, near Greenville, where he owned a 1,000 acres and built two large identical houses, one for himself and the other for his wife—though the couple seemed to be on good terms.

Thompson filled his house with Mexican memorabilia and employed a full-time gardener to care for exotic plants and shrubs he had collected.

The Florida legislature appointed him solicitor general of a circuit in 1868, but in 1868 he died while in Tallahassee, and he was buried in the churchyard of St. John's Episcopal Church there.