Rising prices and the financial Panic of 1837 led to an economic depression in the city. In this situation Clark won office against the disunited Democrats. While Mayor, Clark advocated formation of an armed municipal police force and sought to discourage the growing tide of impoverished Europeans pouring into the city. His proposals for curbing immigration would be considered protectionist or xenophobic today: special taxes on immigrants and the favoring of war veterans and their families for welfare and public jobs. He was re-elected for a second one-year term in 1838 but, helped by a brief economic upturn, a reunited Tammany Hall won back the mayoralty in 1839 and kept it for many years. The Whigs remained an important political force in municipal politics for another 15 years. However, after 1854, the Whig Party split into northern and southern factions over the issue of slavery and gradually disintegrated, with most northern Whigs eventually joining the new Republican Party. Prominent Whigs who later became Republicans included Abraham Lincoln and William Seward.
After he was defeated for a third term, Clark devoted himself to banking and insurance interests and became an enthusiastic supporter of Hamilton College, where an annual prize for oratory was established in his honor. Four years of elocution classes are no longer required of all graduates, but the Clark Prize is still awarded.
In Albany on 18 May 1815, he had married Catherine Maria Lamb, daughter of his 1812 colleague General Anthony Lamb. They had six children, five of whom survived their mother’s early death in New York City on 23 April 1832. After having been a widower for almost 30 years, Clark died on 2 August 1861 at his home in Brooklyn. He is buried with Catherine Maria, their daughter Agnes Reid, and several grandchildren in Vault #89 of the New York Marble Cemetery.