The parkway proceeds northward through the Town of Islip as a four-lane divided highway, passing through residential parts of the adjacent hamlet of Brentwood to reach exit S3, a partial cloverleaf interchange with Pine Aire Drive.

Continuing northward through Islip, the Sagtikos Parkway leaves Brentwood ahead of exit S2, a connection to County Route 13 (CR 13, named Crooked Hill Road).

The part between the Southern State and Pine Aire Drive handled an average of 87,250 vehicles per day; slightly lower numbers were recorded along the segment between Pine Aire Drive and the Long Island Expressway, with roughly 85,300 vehicles using the section on a daily basis.

The portion between the Long Island Expressway and the Northern State Parkway carries an average of 67,600 vehicles per day.

In order to construct the freeway, the heirs of the late David Gardiner, who owned the historic Sagtikos Manor in West Bay Shore, donated 197 acres (80 ha) of land to the Long Island State Park Commission (LISPC).

Robert Moses commented that the completed parkway reflected LISPC's objective to construct well-designed recreational facilities.

[2] From 1997–2001, engineers from NYSDOT worked on a $6.5 million (2001 USD) study aimed to improve Long Island's transportation system by 2020.

[12] In 2002, the Wolkoffs, a family of real estate developers, bought land used by the Pilgrim Psychiatric Center for $20 million (2002 USD) with the intent of redeveloping the property as a new smart growth community named Heartland Town Square.

[13] The community, situated near the interchange between the Sagtikos Parkway and the Long Island Expressway (I-495), would have 9,000 housing units and various commercial & recreational buildings.

[15] In response, the study suggested that a third lane be constructed along the Sagtikos from the Southern State Parkway to the Long Island Expressway.