The following is a listing of US casualties in the various conflicts that have been a part of the country's history. The following numbers reflect only reported war deaths and exclude those wounded and/or missing. The Civil War maintains the highest American casualty total of any conflict.
In its first 100 years of existence, over 683,000 Americans lost their lives, with the Civil War accounting for 623,026 of that total (91.2%). Comparatively, in the next 100 years, a further 626,000 Americans died through two World Wars and several more regional conflicts (World War 2 representing 65% of that total). Using this comparison, the Civil War might very well be the most costly war that America has ever fought.
Sources: U.S. Army Military History Institute; iCasualties.org; Wikipedia