Karnes's areas of principal activity included federal, state, and international relations, corporate law, real estate, and financial institutions.

[citation needed] His governmental and later business experience involved many areas which were germane to Kutak Rock's finance and structured transaction practices, as well as a very broad range of clients and special issues.

[citation needed] Running in his own right in 1988, Karnes successfully captured the Republican nomination against Congressman Hal Daub, but lost to former governor Bob Kerrey, a Democrat, in the general election.

Karnes made a memorable faux pas when, during a campaign stop at the Nebraska State Fair, he said, "What this nation needs is fewer farmers.

[2] Karnes served on the boards of, or acted as an advisor to, publicly traded U.S. companies, including Fannie Mae, Data Transmission Network Corporation, and RJT Securities, Inc.

He served on the Omaha Airport Authority board,[2] and was a director of several private companies, including Frontier Bank, FSB of Park City, Utah, El Paseo Bank of Palm Desert, California, Orion Healthcare Corporation (healthcare technology), Waitt Media, Inc. (broadcasting, commercial advertising and entertainment), Tri Med Research, Inc. (medical technology), Farnam Group, Inc. (multifamily real estate development), Regency Court, L.L.C.

[citation needed] In January 2016, Karnes endorsed New Jersey governor Chris Christie for president in that year's election.

[6] On June 14, 2008, Karnes married Kristine Dorn, a partner at Kutak Rock and 1998 Graduate of Creighton University School of Law.