The first settlers of the area which would eventually become Homewood arrived in the early 1800s. The area's population, however, did not grow significantly until Birmingham suffered a major cholera epidemic in 1873. People soon began buying up land and developing communities surrounding Birmingham. Many of the smaller communities which would eventually become Homewood were developed during this time period, including Rosedale, Grove Park, Edgewood, and Oak Grove. Edgewood saw the greatest amount of development. The community contained an Electric Railway leading to downtown Birmingham by 1911 and a man-made lake by 1915. In 1926, a local attorney named Charles Rice started a movement to merge several of the communities surrounding Birmingham. In September of the same year, Rosedale, Edgewood, and Grove Park voted to incorporate under the name Homewood. The city of Hollywood, Alabama was annexed into Homewood in 1929. In 1955, Oak Grove was also annexed into Homewood. The Great Depression and a polio epidemic, which sickened 80 children in Homewood, greatly damaged Homewood's economy and social landscape. The regional economy picked up after the outbreak of World War II and the accompanying steel boom in Birmingham, where production ramped up in order to contribute to the war effort. During the 1940's, Homewood's police and fire departments doubled in size to accommodate a 75% increase in the city's population from 1940 to 1950. 

In 1959, Homewood voters defeated a move by Birmingham to annex the city. A second attempt supposedly succeeded in July 1964, but voting irregularities and lawsuits prevented the outcome of that election in the courts until September 9, 1966, when the Alabama Supreme Court ruled the 1964 vote null and void. In a special election on December 13, 1966, a vote for annexation failed with 65% of Homewood residents voting against the annexation.  In 1970, Homewood created its own school system, breaking away from Jefferson County. According the latest census, the City of Homewood has approximately 25,600 residents, 10,820 households and 5,450 families living in the city limits.