It is named after Alexander Lindsay, a lawyer who lived in South Buffalo and commuted to work in Pittsburgh; he successfully lobbied for the city to be connected to the proposed Keystone Shortway (I-80).

[4] PA 28 begins adjacent to Downtown Pittsburgh at Anderson Street near the Interstate 279 (I-279)/I-579 interchange and travels north/northeast along the northern bank of the Allegheny River.

Upgrades in 2013 made it a limited-access highway throughout its 44.5 miles (71.6 km) in the Pittsburgh metropolitan area from the route's start at I-279 to Rayburn Township, Armstrong County, with Governor Tom Corbett attending the completion ceremony on November 17, 2014.

At exit 19, PA 28 merges with the limited-access US 422 and heads east along US 422 as it proceeds south of West Kittanning.

[6] Upon crossing the Allegheny River and entering Kittanning, US 422 and PA 28 interchange with Pennsylvania Route 66.

PA 66 then joins the concurrency for two miles (3 km) to an exit with U.S. Route 422 Business southeast of downtown Kittanning.

After the split, PA 28 heads northeast as Broad Street paralleling Redbank Creek.

In Hawthorn, PA 28 is called Brookville Street and meets the western terminus of Pennsylvania Route 536.

Then after crossing North Fork Creek, US 322/PA 28 meet the southern terminus of the former Pennsylvania Route 968.

East of Brookville in Pine Creek Township, PA 28 intersects Interstate 80 at exit 81 a diamond interchange.

In Brockway, PA 28 is called Main Street before terminating (ending) at a "T" intersection with U.S. Route 219.

[7] By 1930, the roadway had been paved from Skyline Road to PA 18, and the segment from Blawnox to Cheswick had been opened to traffic.

[12] In 1958, construction began on another stretch of freeway between PA 8 north to the Highland Park Bridge interchange.

[10] In 1964, the roadway to Blawnox was opened, also part of this project was the reconstruction of the segment from Brackenridge and Butler to expressway standards.

[7] On October 17, 1980, the expressway from Exit 12 to the north border of Tarentum was opened to traffic, it was also extended onto a new at-grade segment.

Construction began on September 6, 1988, and involved blasting 600,000 cubic yards of rock from the hillside that parallels the highway to reduce slides, widening the lanes to 12 feet each, adding 10-foot-wide shoulders, adding should pull-off areas such as on the eastern segment, and placing a Jersey barrier in the middle of the four foot median.

The $14.4 million project that required four lanes of traffic to squeeze into two finally came to an end on December 7, 1990, due to rain hampering construction.

Glare screen was erected on the Jersey barrier in 1991 to cut down on the effects of headlights from oncoming traffic.

[7] On May 20, 1996, an act of the Pennsylvania legislature officially renamed the Allegheny Valley Expressway as the Alexander H. Lindsay Highway.

[15] In March 2007, a project to add a southbound truck climbing lane from Harmar and Harwick began.

Ater this was completed, the through lanes were demolished and rebuilt from the ground up, and the ramp from PA 8 south was permanently closed and replaced by a new, differently constructed one.

It consisted of roadway reconstruction, bridge replacement, bridge rehabilitation, wall construction, approach roadway widening, drainage, guide rail, concrete barrier, curb, landscaping, highway lighting, signing and pavement markings, signals, and improvements between Exit 4 and Exit 5.

[7] In November 2009, a project began to rebuild the at-grade interchanges on East Ohio Street.

The $24.8 million project included demolishing and relocating the Norfolk Southern rail lines, upgrading drainage, replacing the wired traffic signals with overhead gantry ones, utility reconstruction, and wall and bridge replacement along PA 28 from Chestnut Street to the 40th Street Bridge.

[25] In its 2015 transportation plan, the Pennsylvania Turnpike Commission (PTC) announced it was interested in building an extension of the Expressway to I-80.

As Route 28 travels through the Brookville city center, it becomes a narrow main street and features a relatively sharp turn just west of the bridge over North Fork Creek.