[3] It carries the hidden designation of State Route 404 (SR 404) for its entire length.

The westernmost segment in Macon is part of the Fall Line Freeway, a highway that connects Columbus and Augusta.

This segment may also be incorporated into the proposed eastern extension of I-14, which is currently entirely within Central Texas and may be extended to Augusta.

In the east-central part of Macon, I-16 travels through Ocmulgee Mounds National Historical Park but without direct access.

I-16 curves to the east-southeast and enters Bleckley County just before it has an interchange with SR 112 just south of Allentown.

The Interstate curves back to the southeast and crosses under SR 278 before it travels south of Montrose.

On the southern edge of the city are interchanges with US 319/US 441/SR 31 and SR 19 (Martin Luther King Jr. Drive).

Just after crossing over some railroad tracks of Norfolk Southern Railway, it enters the city limits of Oak Park.

At an interchange with SR 307 (Dean Forest Road), I-16 begins traveling along the Savannah–Garden City line.

It crosses over the Springfield Canal just before a partial interchange with the former eastern terminus of SR 204 (West 37th Street).

I-16 curves to the north-northeast and reaches its eastern terminus, an interchange with Montgomery Street in downtown Savannah.

The road is designed for contraflow travel with railroad-type gates to block most entrance and exit ramps for the normally eastbound lanes.

During hurricane evacuation, I-16 is converted into westbound traffic from Savannah to west of US 441 in Dublin (exit 51), a total of 125 miles (201 km).

[16] The last part of the I-16 opened on September 22, 1978, placing it in Emanuel, Candler, and Bulloch counties and completing the connection between downtown Macon and Savannah.

As a result, the eastbound I-16 lanes from Savannah to US 1 (exit 90) were opened to westbound traffic.

[19][20] Until 2000, the state of Georgia used the sequential interchange numbering system on all of its Interstate Highways.

[21] In 2001, the Georgia General Assembly passed a resolution to designate the Earl T. Shinhoster Interchange at the interchange with Martin Luther King Jr. Boulevard in Savannah in honor of Earl Shinhoster,[22][23] who was a black civil rights activist.

[24] In 2003, the Georgia General Assembly passed a resolution to designate I-16 in honor of James L. Gillis Sr.,[25] a Democrat who served as a state representative, state senator, and director of the Georgia Department of Transportation, as the Jim Gillis Historic Savannah Parkway.

[citation needed] Gillis's sons, Hugh and James Jr., also served as Democratic state legislators.

[29] Due to this, people had to take detours up to 10 minutes longer than the normal route through the towns of Adrian and Soperton.

Due to high congestion during rush hour in Savannah and many deadly car accidents, the Georgia Department of Transportation (GDOT) has undertaken a new construction project at the interchange of I-95 and I-16 (exit 157 on I-16), along with other I-16 improvements.

[36] However, construction did not start until 2020, has been delayed multiple times, and is now expected to cost $317.4 million.

[43] Three additional phases are included in the project, which ultimately are intended to help improve access to and from downtown Macon[46] and Gray Highway[47] via the currently-underutilized Second Street bridge, reducing congestion on Spring Street and North Avenue:[45] Also as a part of this project, GDOT spent $12 million in the Pleasant Hill neighborhood to help mitigate the effect of the construction and new highway ramps.

The construction, which was completed in the summer of 2018, included the creation of two new parks and the transformation of Penniman House, the childhood home of the late musician Little Richard, into a community resource center.

[49] In Savannah, city and state officials are currently considering removing the Earl T. Shinhoster Bridge, which carries eastbound traffic over Martin Luther King Jr. Boulevard and onto Montgomery Street at the eastern terminus of I-16.

The construction of the I-16 flyover ramps into Savannah in the 1960s led to the removal of Union Station, as well as two full city blocks, which had severe negative impacts on the African American community.

A study about possibly removing the ramps was approved and funded by the Savannah City Council in December 2023.

Senators Jon Ossoff and Raphael Warnock announced that $1.8 million in federal funding had been allocated toward the planning of the project.

As its number suggests, it is a spur from SR 404, the unsigned route that is designated along the full length of I-16.

[56]Interstate 516 (I-516) is a 6.49-mile-long (10.44 km) auxiliary route from SR 21 (Augusta Road) in Garden City to DeRenne Avenue in Savannah.