SR 253 is a northwest–southeast highway that connects Harrisonburg with Cross Keys and Port Republic in southeastern Rockingham County.

The state highway also provides access to portions of James Madison University on either side of Interstate 81 (I-81).

Port Republic Road was expanded to four lanes within Harrisonburg in the mid-1990s and mid-2000s and along a short stretch south from the city limits in the early 2010s.

SR 253 begins at an intersection with US 11 (Main Street) south of downtown Harrisonburg and southwest of the campus of James Madison University.

SR 253's next intersection is with Forest Hill Road, which leads to the James Madison University Convocation Center, the Edith J.

SR 253's center left-turn lane ends and the road expands to a four-lane divided highway at the boundary between the independent city of Harrisonburg and Rockingham County.

[7] As of 1932, the remainder of Port Republic Road followed highways maintained by the city of Harrisonburg and Rockingham County.

[8] By July 1933, after the passage of the Byrd Road Act that established Virginia's secondary highway system and transferred maintenance responsibility for local highways from the county to the state, all of Port Republic Road's route numbers changed.

[27][28][29] Port Republic Road in the city of Harrisonburg and SR 659 in Rockingham County from the city to US 340 were transferred from the secondary system to the primary highway system as SR 253 by a resolution passed by the Commonwealth Transportation Board on March 17, 2005.

[2][29] The transfer was supported in part by the planned relocation of Rockingham Memorial Hospital from north of the James Madison University campus in the city to southeast of the city in Rockingham County, a process that began in 2004 and was completed when the hospital opened in 2010.