European heritage
The area has been grazed since the 1860s. Following the passing of the NSW Crown Lands Alienation Act of 1861, which provided for the legal purchase and occupation of Crown lands, the Brennan family of Irish immigrants established a house on a terrace above Tuggeranong Creek. The remnants of a house site, probably the home of the Brennan family, can be found to the east of Tuggeranong Creek. In 1937, most of the land became part of the Melrose Valley Station.
A former travelling stock reserve in the north-east of the reserve adjacent to the NSW border, is listed on the ACT Heritage Register. The Melrose travelling stock reserve was about 7 hectares in area. Cattle were able to be moved from properties in the Tuggeranong Valley along the Old Tuggeranong Road to the Tuggeranong railway siding nearby for transportation as far away as Sydney. The travelling stock reserve was originally established to receive stock waiting to be loaded onto, or that had been unloaded from, trains but has not been grazed by stock for several decades now.
Part of Melrose Nature Reserve's eastern boundary is the NSW border, which is followed by the old Bombala Railway Line just inside NSW. Sections of this line southward from Queanbeyan were completed in stages from 1887 to 1921. The last passenger service on the line was in 1988 and the last freight in 1989.
Melrose Nature Reserve was established in 1993.