Running primarily north to south for approximately 1,273 kilometres (791 mi), it is the longest and busiest highway in the province carrying more than 180,000 vehicles per day near Downtown Calgary.

In Calgary, the route is a busy freeway named Deerfoot Trail that continues into central Alberta as the Queen Elizabeth II Highway, bypassing Red Deer.

In Edmonton, it is briefly concurrent with freeway sections of Highways 216 and 16 before bisecting St. Albert and reverting to two lanes en route to Athabasca.

Major changes include the construction of a divided expressway between Calgary and Edmonton in the 1960s, realignment along Deerfoot Trail in the 1980s, and twinning south of Nanton in the 1990s.

[3] Several projects including median widening and interchange upgrades have been undertaken in the 2010s to increase the safety of the highway's busier sections, with further improvements either under construction or awaiting funding.

During the winter, accidents are common on the stretch of the highway between Calgary and Edmonton as the weather can change rapidly and drivers underestimate the conditions, overwhelming emergency services attempting to respond.

[5] Between Fort Macleod and Morinville, Highway 2 maintains no fewer than four lanes of traffic and is largely a freeway between Okotoks and Edmonton, with improvements underway to eliminate the at-grade crossings that remain.

It is a popular stop for travellers and truckers including fuel stations and food establishments on either side of the highway, accessible via the interchange at McKenzie Road.

[9] It crosses the river alongside a railroad bridge, then curves north to interchanges with Highways 11 and 11A, leading west to Rocky Mountain House and Sylvan Lake, respectively.

[23] Five separately named routes are designated as Highway 2 in the cities of Edmonton and St. Albert, denoted by varying levels of signage.

Signage directs traffic destined for Lloydminster, Cold Lake, and Fort McMurray to use the southeast portion of Henday to reach Highway 16 north of Sherwood Park.

Highway 88 follows the east bank of Lesser Slave Lake before a long journey north to Fort Vermilion.

At Driftpile the highway crosses a river of the same name en route to High Prairie at the west end of Lesser Slave Lake.

At the south end, the highway is a lightly travelled two-lane road from the United States border to Fort Macleod.

[40] Within Calgary, volume climbs exponentially on Deerfoot Trail through the southern suburbs of the city reaching more than 170,000 vehicles per day at Memorial Drive near downtown, making that stretch of Highway 2 the busiest roadway in western Canada.

Volume swiftly drops north of Beddington Trail in Calgary, but remains moderate on the Queen Elizabeth II Highway until Edmonton where it again increases to nearly 100,000 vehicles per day south of the city.

Volume remains very light through most of the Peace Country before briefly exceeding 20,000 vehicles per day near the northern terminus in Grande Prairie.

[42] Deerfoot Trail in Calgary is also prone to a higher than average number of collisions due to its high volume and concentration of interchanges within a relatively short distance.

[43] Alberta Transportation has established several zones on the Queen Elizabeth II Highway where the 110 km/h speed limit is enforced by aircraft.

[47] In 2016, Leduc proposed photo radar speed enforcement on Highway 2 between the south end of the city and Edmonton's southern limit to catch excessive speeders, pending provincial approval.

[50] Leduc mayor Greg Krischke said that the project is not a "cash cow" and the primary objective is to reduce excessive speed and increase safety for first responders.

[50] An Alberta Transportation study shows that 100,000 vehicles exceeded 140 km/h (87 mph) on the stretch in 2015, and Krischke said that drivers who do not want tickets should abide by the speed limit.

[54] It was a gravelled highway that ran from the US border at Carway directly through Macleod, Calgary, Red Deer and Edmonton to Clyde where it became a dirt road.

Plans were developed in the late 1950s for a new four-lane superhighway to connect Calgary and Edmonton, creating a safer route that would bypass most of the communities along the way.

Several projects including median widening and interchange upgrades were completed in the 2010s that increased the safety of the highway's busier sections.

In the early morning hours of December 15, 2011, a Lethbridge man killed three people on Highway 2 immediately north of Claresholm.

The only set of traffic lights on this CANAMEX section are in central Claresholm;[65] a bypass is proposed that would carry Highway 2 to the east of town on a new free-flowing alignment.

[69] In Calgary, where Highway 2 (Deerfoot Trail) experiences heavy congestion at peak hours, a major planning study is underway to determine the best course of action for upgrades to the freeway.

[78] Between Edmonton and Leduc, Alberta Transportation has drafted plans to construct a dual freeway system in conjunction with a second ring road approximately 8 km (5 mi) beyond Anthony Henday Drive.

Between Edmonton and 41 Avenue SW, the highway would be realigned several hundred metres to the west to facilitate construction of a large interchange with the outer ring road.