He gave an impassioned speech in San Antonio in December 1860, strongly opposing secession and calling for the "perpetuity of the national Union."

Anderson was elected the seventh lieutenant governor of Ohio in late 1863 and took office the following year.

Ohio historian Dwight L. Smith wrote that his brief term in office was "uneventful... [and] the services he performed were merely routine."

After leaving the governorship, Anderson resumed his legal practice and moved back to Kentucky, where he died at the age of 81.

Another brother, William Marshall Anderson, was a noted explorer, politician, and briefly a member of the New Virginia Colony of ex-Confederates in Mexico during the reign of Emperor Maximilian.