He studied law, moved west and commenced practice in a settlement in 'Black Hawk Purchase', Wisconsin Territory, that was later incorporated as Burlington, Iowa.

In 1861, Grimes was a member of the peace convention held in Washington, D.C., in an effort to devise means to prevent the impending Civil War.

[2] During President Andrew Johnson's impeachment trial, Grimes broke party ranks, along with six other Republican senators and voted for acquittal.

Senators William Pitt Fessenden, Joseph S. Fowler, Grimes, John B. Henderson, Lyman Trumbull, Peter G. Van Winkle,[citation needed] and Edmund G. Ross of Kansas, who provided the decisive vote,[3] defied their party and public opinion and voted against convicting Johnson because they were disturbed by how the proceedings had been manipulated in order to give a one-sided presentation of the evidence.

In Butler's hearings, and in subsequent inquiries, there was increasing evidence that some acquittal votes were acquired by promises of patronage jobs and cash cards.