James Ruse Drive is a 6.4-kilometre-long (4.0 mi) limited-access urban highway located to the east and north of Parramatta, in Western Sydney, New South Wales, Australia. Originally a series of disconnected urban streets, it was later upgraded to act as a bypass of central Parramatta.

James Ruse Drive commences at the intersection with Parramatta Road in Clyde and heads as in a northerly direction as a dual-carriageway, 6-lane highway, crossing under M4 Motorway and then nearly immediately over the Parramatta Light Rail. It then crosses over the Parramatta River, through an interchange with Victoria Road and another interchange with Kissing Point Road and Pennant Street, where it narrows to a four-lane road, and continues in a north-westerly direction to the interchange with Pennant Hills Road, where it widens again to a six-lane road and becomes part of Cumberland Highway. It continues in a westerly direction to end at the interchange with Windsor Road in Northmead; the road continues west as Briens Road, part of Cumberland Highway.

The road was named in honour of James Ruse, a convict who was given land in the Parramatta district, which he successfully developed into the colony's first sustainable farm. The original Experiment Farm Cottage still exists on Ruse Street, Parramatta.

In the early 20th century, only suburban streets existed along today's route. Starting at Parramatta Road, it headed north as Berry Street, crossed the Carlingford railway line and changed name to Aston Street, and continued north until reaching the Parramatta River. On the other side, Rydalmere Avenue headed north until terminating at Kissing Point Road.

The passing of the Main Roads Act of 1924 through the Parliament of New South Wales provided for the declaration of Main Roads, roads partially funded by the State government through the Main Roads Board (MRB). Main Road No. 309 was declared on 8 August 1928, from the intersection with Parramatta Road in Clyde along Berry and Aston Streets until it reached the Carlingford railway line; with the passing of the Main Roads (Amendment) Act of 1929 to provide for additional declarations of State Highways and Trunk Roads, this was amended to Main Road 309 on 8 April 1929.

A pre-stressed concrete bridge was built over the Parramatta River to link Aston Street and Rydalmere Avenue, completed in 1966. Main Road 309 was extended north along the full length of Aston Street over the new bridge and along Rydalmere Avenue to end at Kissing Point Road on 22 February 1967.

The Parramatta Bypass project was constructed in stages. The first 1.5 kilometre section extending Rydalmere Avenue from Victoria Road to a new interchange with Pennant Hills Road opened on 6 June 1977. The next 1.6 kilometre section extending Rydalmere Avenue from Pennant Hills Road to a new interchange with Windsor Road opened on 10 September 1979. Stage 3 along Briens Road from Windsor Road to Kleins Road opened 19 September 1980, followed by Stage 4 along Briens Road to Old Windsor Road on 21 December 1980. The eastern half of the Parramatta Bypass (along Berry and Aston Streets, and Rydalmere Avenue and its new extensions to Windsor Road) was named as James Ruse Drive on 2 February 1981. The elimination of the railway crossing with an overpass where it crosses A'Becketts Creek was finished in May 1984.

With the declaration of Cumberland Highway on 26 August 1988, State Highway 13 was altered to use the new route from its northwestern end at the interchange with Windsor Road to the interchange with Pennant Hills Road at North Parramatta; the northern end of Main Road 309 was extended north along James Ruse Drive to meet State Highway 13 at the same interchange. In July 1994, as part of a grade separation project, a bridge was built over James Ruse Drive at Rydalmere to eliminate the intersection with Victoria Road.