Pratt served as a member of the Maryland House of Delegates from 1832 to 1835, and as a presidential elector on the Whig ticket for William Henry Harrison in 1836.

He campaigned with the promise of resolving the serious state debt, and defeated his opponent, James Carroll, by a margin of a mere 548 votes.

The most serious problems of Pratt's administration came with relations to the northern neighbor state of Pennsylvania, which refused to comply with the Fugitive Slave Law.

Two more incidents of this nature occurred during Pratt's tenure as governor, one involving the death of a slaveholder who was ambushed in Pennsylvania by abolitionists as he and his party returned to Maryland with their re-captured slaves.

Pratt's term as governor expired in 1848, and he briefly returned to practicing law in Annapolis, Maryland.

As senator, Pratt supported Democrat James Buchanan in the 1856 presidential election, following the dissolution of the Whig party.

When the American Civil War began, Pratt was eyed suspiciously by Maryland authorities, as he was staunchly pro-slavery, but mostly pro-South, and even gave a son to the Confederate Army.