Macon was founded on the site of the Ocmulgee Old Fields, where the Creek Indians lived in the 18th century. Their predecessors, the Mississippian culture, built a powerful agriculture-based chiefdom (950–1100 AD). The Mississippian culture constructed earthwork mounds for ceremonial, religious, and burial purposes. Indigenous peoples inhabited the areas along the Southeast's rivers for 13,000 years before Europeans arrived.

Macon was developed at the site of Fort Benjamin Hawkins, built in 1809 at President Thomas Jefferson's direction after he forced the Creek to cede their lands east of the Ocmulgee River. (Archeological excavations in the 21st century found evidence of two separate fortifications.) The fort was named for Benjamin Hawkins, who served as superintendent of Indian Affairs for the Southeast territory south of the Ohio River for more than 20 years, had lived among the Creek, and was married to a Creek woman. Located at the fall line of the Ocmulgee River, the fort established a trading post with native peoples at the river's most inland point navigable from the Low Country.

Fort Hawkins guarded the Lower Creek Pathway, an extensive and well-traveled American Indian network that the U.S. government later improved as the Federal Road, linking Washington, DC, to the ports of Mobile, Alabama, and New Orleans, Louisiana. Used for trading with the Creek, the fort also was used by state militia and federal troops. It was a major military distribution point during the War of 1812 and the Creek War of 1813. After the wars, it was a trading post and garrisoned troops until 1821. Decommissioned around 1828, it later burned to the ground. A replica of the southeast blockhouse, built in 1938, stands on an east Macon hill. Fort Hawkins Grammar School occupied part of the site. In the 21st century, archeological excavations have revealed more of the fort, increasing its historical significance, and led to further reconstruction planning for this major historical site.

With the arrival of more settlers, Fort Hawkins was renamed "Newtown". After Bibb County's organization in 1822, the city was chartered as the county seat in 1823 and officially named Macon, in honor of Nathaniel Macon, a statesman from North Carolina, from where many early Georgia residents hailed. City planners envisioned "a city within a park" and created a city of spacious streets and landscapes. Over 250 acres (1.0 km) were dedicated for Central City Park, and ordinances required residents to plant shade trees in their front yards.

Because of the beneficial local Black Belt geology and the availability of slave labor, cotton became the mainstay of Macon's early economy. The city's location on the Ocmulgee River aided initial economic expansion, providing shipping access to new markets. Cotton steamboats, stagecoaches, and the 1843 arrival of the railroad increased marketing opportunities and contributed to Macon's economic prosperity.

Macon's growth had other benefits. In 1836, the Georgia Conference of the Methodist Episcopal Church chose Macon as the location for Wesleyan College, the first U.S. college to grant women college degrees. Nonetheless, Macon came in last in the 1855 referendum voting to be Georgia's capital city with 3,802 votes.

During the American Civil War, Macon served as the official arsenal of the Confederacy manufacturing percussion caps, friction primers, and pressed bullets. Camp Oglethorpe was established as a prison for captured Union officers and enlisted men. Later, it held only officers, at one time numbering 2,300. The camp was evacuated in 1864.

Macon City Hall served as the temporary state capitol in 1864 and was converted to a hospital for wounded Confederate soldiers. Union General William Tecumseh Sherman spared Macon on his march to the sea. His troops sacked the nearby state capital of Milledgeville, and Maconites prepared for an attack. Sherman, however, passed by without entering Macon.

The Macon Telegraph reported the city had furnished 23 companies of men for the Confederacy, but casualties were high. By the war's end, Maconite survivors fit for duty could fill only five companies.

The city was taken by Union forces during Wilson's Raid on April 20, 1865.

Because of its central location, Macon developed as a state transportation hub. In 1895, The New York Times dubbed Macon "The Central City" because of its emergence as a railroad transportation and textile factory hub. Terminal Station was built in 1916. In the 20th century, Macon grew into a prospering town in Middle Georgia.

Macon has been impacted by natural catastrophes. In 1994, Tropical Storm Alberto made landfall in Florida and flooded several Georgia cities. Macon, which received 24 inches (61 cm) of rain, suffered major flooding.

On May 11, 2008, an EF2 tornado hit Macon. Touching down in nearby Lizella, the tornado moved along the southern shore of Lake Tobesofkee, continued into Macon, and lifted in Twiggs County. The storm's total path length was 18 miles (29 km), and its path width was 100 yards (91 m). The tornado produced sporadic areas of major damage, with widespread straight-line wind damage to the south of its path. The most significant damage was along Eisenhower Parkway and Pio Nono Avenue in Macon, where two businesses were destroyed and several others were heavily damaged. The tornado also impacted Macon State College, where almost 50% of the campus's trees were snapped or uprooted and several buildings were damaged, with the gymnasium. The tornado's intensity varied from EF0 to EF2, with the EF2 damage and winds up to 130 miles per hour (210 km/h) occurring near the intersection of Eisenhower Parkway and Pio Nono Avenue.

On July 31, 2012, voters in Macon (57.8% approval) and Bibb County (56.7% approval) passed a referendum to merge the governments of the city of Macon and most of unincorporated Bibb County. The vote came after the Georgia General Assembly passed House Bill 1171, authorizing the referendum earlier in the year; Four previous consolidation attempts (in 1933, 1960, 1972, and 1976) failed.

As a result of the referendum, the Macon and Bibb County governments were replaced with a mayor and a nine-member county commission elected by districts, and a portion of Macon extending into nearby Jones County was disincorporated. Robert Reichert was elected the first mayor of Macon-Bibb in the September 2013 election, which required a runoff with C. Jack Ellis in October.

The Ocmulgee River is a major river that runs through the city. Macon is one of Georgia's three major Fall Line cities, along with Augusta and Columbus. The Fall Line is where the hills of the Piedmont plateau meet the flat terrain of the coastal plain. As such, Macon has a varied landscape of rolling hills on the north side and flat plains on the south. The fall line, where the elevation drops noticeably, causes rivers and creeks in the area to flow rapidly toward the ocean. In the past, Macon and other Fall Line cities had many textile mills powered by the rivers.

Macon is located at 32°50′05″N 83°39′06″W / 32.834839°N 83.651672°W / 32.834839; -83.651672 (32.834839, −83.651672). According to the United States Census Bureau, the city has a total area of 56.3 square miles (146 km), of which 0.5 sq mi (1.3 km) (0.82%) is covered by water. Macon is about 330 ft (100 m) above mean sea level.

Macon has a humid subtropical climate (Köppen climate classification Cfa). The normal monthly mean temperatures range from 46.3 °F (7.9 °C) in January to 81.8 °F (27.7 °C) in July. On average, 4.8 days have 100 °F (38 °C)+ highs, and 83 days have 90 °F (32 °C)+ highs, and 43 days with a low at or below freezing; the average window for freezing temperatures is November 7 thru March 22, allowing a growing season of 228 days.

The city has an average annual precipitation of 45.7 inches (1,160 mm). The wettest day on record was July 5, 1994, with 10.25 in (260 mm) of rain, and the wettest month on record was July 1994, with 18.16 in (461 mm) of rain. Since 1892, though, when precipitation records for the city began, two months, October 1961 and October 1963, did not even record a trace of precipitation in the city, and two other months, October 1939 and May 2007, only recorded a trace. Snow is occasional, with about half of the winters receiving trace amounts or no snowfall, averaging 0.7 in (1.8 cm); the snowiest winter was 1972−73 with 16.5 in (42 cm).

Macon is the largest principal city in the Macon-Warner Robins-Fort Valley CSA, a combined statistical area that includes the Macon metropolitan area (Bibb, Crawford, Jones, Monroe, and Twiggs Counties) and the Warner Robins metropolitan area (Houston, Peach, and Pulaski Counties) with a combined population of 411,898 in the 2010 census.

As of the official 2010 U.S. census, the population of Macon was 91,351. In the last official census, in 2000, 97,255 people, 38,444 households, and 24,219 families were residing in the city. The population density was 1,742.8 inhabitants per square mile (672.9/km). The 44,341 housing units had an average density of 794.6 per square mile (306.8/km). The racial makeup of the city was 67.94% African American, 28.56% White, 0.02% Native American, 0.65% Asian, 0.03% Pacific Islander, 0.46% from other races, and 0.77% from two or more races. Hispanics or Latinos of any race were 2.48% of the population. By the 2020 census, its population increased to 157,346.

Of the 38,444 households in 2000, 30.1% had children under 18 living with them, 33.0% were married couples living together, 25.7% had a female householder with no husband present, and 37.0% were not families. About 31.7% of all households were made up of individuals, and 12.1% had someone living alone who was 65 or older. The average household size was 2.44 and the average family size was 3.08.

In the city, the age distribution was 26.9% under 18, 11.3% from 18 to 24, 27.5% from 25 to 44, 20.0% from 45 to 64, and 14.3% who were 65 or older. The median age was 34 years. For every 100 females, there were 79.7 males. For every 100 females 18 and over, there were 72.8 males.

Prior to 2013, the city government consisted of a mayor and city council. Robert Reichert was elected the first mayor of the consolidated Macon-Bibb County in October 2013. There are also 9 County Commissioners elected from districts within the county.

On March 15, 2019, the U.S. Securities and Exchange Commission charged the former County Manager, Dale M. Walker, with fraud.

Bibb County Public School District operates district public schools.

Public high schools include:

• Central High School
• Howard High School
• Northeast Health Science Magnet High School
• Rutland High School
• Southwest Magnet High School and Law Academy
• Westside High School

Georgia Academy for the Blind, operated by the state of Georgia, is a statewide school for blind students.

Also operated by Bibb County Public Schools:

• Elam Alexander Academy
• Northwoods Academy

Macon is home to several private high schools, many of which were established as segregation academies for parents wishing to avoid the desegration of private schools, with the exception of Mount de Sales Academy.

• Covenant Academy
• First Presbyterian Day School
• Mount de Sales Academy
• Stratford Academy
• Tattnall Square Academy
• Windsor Academy

• The Academy for Classical Education
• Cirrus Academy Charter School

Approximately 30,000 college students live in the greater Macon area.

• Central Georgia Technical College
• Mercer University
• Middle Georgia State University
• Miller-Motte Technical College - satellite campus
• Wesleyan College