The original inhabitants of the area were Onondaga clans, whose village was atop a hill on the eastern border of Onondaga territory along what is now Kinne St. An established trail ran down part of what is now James Street to Ley Creek where the Onondagas could travel by canoe to their capital along the northeast shore of Onondaga Lake.
Portions of this Onondaga village dating from the early eighteenth century were uncovered in the 1930's when East Syracuse High School was being built on Kinne St. near James.
In the 1870's, the main line of the New York Central Railroad was built through the northern part of Messina, and the DeWitt Rail yards complex, one of the busiest in the world in its day, stretched from Messina five miles east to Minoa.
During most of the nineteenth century the larger part of the hamlet was south of the railroad yards, but as the population grew with rail workers, housing expanded to the north. In the 1960's, Interstate 690 was built through the southern part of the Village between the railroad and Erie Blvd, which was built over part of the old canal. Now only a small portion of the original settlement south of the railroad remains, including about 100 of the Village's 1400 dwelling units.