His father was David Walker, a prominent early Kentucky politician who served in the U.S. House of Representatives.

David S. Walker was a cousin and close business and political confidante of Florida territorial governor Richard K. Call.

He was also related to Florida Senator Wilkinson Call, who was Walker's law partner for several years in the 1850s and 1860s in Tallahassee.

Walker entered politics as a Whig and was elected to the first session of the Florida State Legislature in 1845, serving Wakulla and Leon Counties as a senator.

[6] During his governorship, Florida transitioned from the federal oversight and military occupation of Reconstruction to readmission into the Union.

He protested the election of the 1868 Constitutional Convention, which was convened to adopt a new government that the Republican U.S. Congress would approve.