Stonewall Jackson biographer James Robertson Jr. heads the list of speakers at Friday's opening ceremonies.
The lectures and battlefield hikes culminate Monday with a commemoration on the anniversary date.
The battle along Antietam Creek on Sept. 17, 1862, was the bloodiest day of combat on U.S. soil. More than 23,000 Union and Confederate soldiers were reported killed, wounded or missing during 12 hours of fighting with no clear winner.
Gen. Robert E. Lee withdrew his troops to Virginia the next day. The Confederate retreat gave President Abraham Lincoln the political strength to issue a preliminary Emancipation Proclamation five days after the battle.