Due to its status as a former Ontario 400-series highway when it was previously the eastern segment of the QEW, and because of its more recent design (rebuilt in the late 1960s), this section was built to higher standards than the Metro-constructed Gardiner and has a speed limit of 100 km/h.

East of Grand Avenue, the freeway crosses Park Lawn Road and a CN rail line, then it curves as it passes the residential condominium towers of The Queensway – Humber Bay neighbourhood along the waterfront, the Mr. Christie cookie factory (which later became a part of Mondelēz International) and the Ontario Food Terminal on the north side.

From Dufferin to Strachan Avenue, the highway is flanked by light industry and a wall of residential towers in the Liberty Village neighbourhood to the north and the buildings of Exhibition Place on the south side.

Between York and Yonge Streets, the highway is flanked by the downtown skyscrapers of the South Core and eastern Harbourfront area, and passes the Scotiabank Arena.

From 2002 to September 2021, the highway's elevated section descends to ground level via the Logan Avenue Ramp where it merges with Lake Shore Boulevard before a signalized intersection with Bouchette Street.

The highest point of the elevated section is the eastbound ramp from the Gardiner to the Don Valley Parkway which goes up and over the westbound lanes, then drops to ground level.

The route of the Expressway necessitated the paving over of parkland, demolition of residences and a popular amusement park, and a long elevated section to get through the downtown area.

Another reason for the proposal to build the lake shore highway was the expected opening of the Saint Lawrence Seaway and the need for adequate roadways to serve the expanded port facilities.

Efforts made by community groups over the next 20 years to restore access to the lake shore, including plans to cover the section of the Expressway and railway line, did not come to fruition.

[43] East of Fort York, the Gardiner was built entirely as an elevated route, through a predominantly industrial area, to the south of railway lands to reach downtown.

It was instead constructed as an elevated section overhead of Lake Shore Boulevard and at its eastern end forks into a flyover of the Don River mouth and a separate connector to the east.

The design left the eastern end open for a future connection with the proposed but never-built Scarborough Expressway, leaving this segment a spur route.

[47] Metro Council approved the renaming in August 1957:[48] After we had finished arguing with [The Board of Trade], Courtland Elliot, the president, made his annual report.

The old Gardiner and Lake Shore Boulevard bridges over the Humber River, which had been in service since the 1950s, were removed and replaced by new structures from 1998-1999, at a cost of CA$100 (equivalent to $169.11 in 2023) million.

Fatal collisions had occurred at the location, including an August 13, 1995, incident where a speeding automobile going eastbound became airborne and collided with a vehicle in the westbound lanes, killing three people.

Proposals started to be floated for the demolition of the elevated segment with its replacement to be buried underground in a tunnel, although such a course of action would have left the Downtown without an east-west freeway for several years.

On April 1, 1997, the stretch of the Queen Elizabeth Way between Highway 427 and the Humber River was downloaded from the Ministry of Transportation of Ontario to Metropolitan Toronto and was redesignated as part of the Gardiner.

The elevated section between the Don River and Leslie Street known as "Gardiner East", intended for connection to the cancelled Scarborough Expressway, was eventually demolished in 2001.

[71] Two locations, at Fort York Boulevard and near Cherry Street were reinforced to prevent "punch-throughs" (holes) from happening on the road surface, potentially knocking a large piece of concrete to the ground below and causing a dangerous incident for the vehicles above.

[73] In 2009, the City of Toronto commenced a study of the York/Bay/Yonge off-ramps and the Bay Street on-ramps "to support and enhance the pedestrian and park spaces in the immediate area while maintaining acceptable traffic capacity and operations".

[80][81] The work is being done in stages and is already in progress: In November 2016, the City of Toronto and mayor John Tory considered imposing a toll to use the Gardiner and the Don Valley Parkway, to cover the maintenance costs of the highway and support public transit construction.

It determined that the combination of the Gardiner Expressway, Lake Shore Boulevard and railway uses tilted the land use to too much of a corridor use, and impacted negatively on the usage of the area.

City staff pointed out that the tunnel would have to avoid several obstacles, including:[88] The proposal planned to put tolls on the new roadway to pay for the cost of building it and to reduce the traffic but it refused (2017 update).

[100] The construction of the realigned Lake Shore Boulevard and the related Gardiner ramp changes is slated for after 2014, after completion of a detailed environmental assessment for the parkland and roadway project.

[103] In May 2008, Waterfront Toronto (the former TWRC) proposed the demolition of the segment from Jarvis Street to the Don River and construction of a widened Lake Shore Boulevard in the style of University Avenue at a projected cost of $200 to $300 million.

To build support for the "hybrid" option among Councillors, Mayor Tory added proposals to direct City staff to study the routing of the connection to the Don Valley Parkway to try to retain as much development potential as possible compared to the "remove" option and report on the feasibility of tunnelling the section, something not even covered in the studies, and which would require a new environmental assessment and possibly a further delay.

The Ride for Heart closes the Gardiner Expressway east of the Humber River and the entire length of the Don Valley Parkway in both directions and is typically held on the first Sunday in June from 2am to 2pm.

[122] The annual closure of the Gardiner Expressway and Don Valley Parkway for Ride for Heart has been criticized for the amount of disruption it causes and its impact on traffic congestion.

[124] On March 5, 2007, a section of the Gardiner Expressway was closed between Spadina Avenue and Jarvis Street due to the threat of ice about the size of a kitchen table falling from the CN Tower.

City crews were quickly sent to close off lanes of traffic to begin an inspection of the structure, which is a late 1960s post-tensioned design built by the province while it was still part of the QEW.