He became an ally of Thomas Hart Benton and Francis Preston Blair Jr. in the struggle for control of the state Democratic Party against pro-slavery forces.

After the war, Brown strongly opposed President Andrew Johnson's Reconstruction policies and supported the Freedmen's Bureau bills.

Seeking to avoid splitting the vote of opponents to President Ulysses S. Grant's re-election, the 1872 Democratic National Convention subsequently nominated the Liberal Republican ticket.

He graduated from Transylvania University in Lexington in 1845 where he was a member of Beta Theta Pi fraternity, and from Yale College in New Haven, Connecticut, in 1847.

There he joined his cousin, Francis P. Blair Jr., and Senator Thomas Hart Benton in a struggle against the pro-slavery faction for control of Missouri's Democratic Party.

On August 26, 1856, he fought a duel on Bloody Island (Mississippi River) with Thomas C. Reynolds (then the St. Louis District Attorney) over the slavery issue.

He recruited over 1,100 soldiers for his regiment, many of whom were St. Louis-area German-Americans, a key constituency that Brown courted for his political advantage.

Brown resigned from the Army after he was elected in late 1863 as a Radical Unionist to the U.S. Senate to fill the vacancy caused by the expulsion of Waldo P. Johnson.

Brown opposed Abraham Lincoln's moderation and objected to the Emancipation Proclamation because it did not free slaves in Missouri and other loyal border states.

Following Lincoln's assassination, Brown was vehemently opposed to new President Andrew Johnson's moderate plan of Reconstruction.

Brown was one of the contenders for the Liberal Republican presidential nomination, but lost to newspaper editor Horace Greeley.