In 1860, Cowan was a delegate pledged to Simon Cameron at the Republican National Convention, and backed Cameron until Cameron gave his support to Abraham Lincoln. In early 1861, Cowan was the Cameron-backed candidate for a U.S. Senate seat, and won the election held by the Pennsylvania legislature. He served one term, 1861 to 1867, and was chairman of the Committee on Patents and the Patent Office for most of his Senate career. Cowan became a supporter of Andrew Johnson's plan for post-Civil War Reconstruction, which cost him the support of Cameron's Republican organization in Pennsylvania. Cowan was defeated for reelection to the Senate, and Radical Republicans who opposed Johnson then blocked Cowan's appointment as U.S. Minister to Austria.