The 601 ran from Gardenvale to the city via Orrong Rd, Commercial Rd and St Kilda Rd through the suburbs of Gardenvale, Elsternwick, Toorak and South Melbourne to the city. The terminus was originally in Swanston St but was moved to Queen St in the late 1980s.
The 601 was originally operated by Melbourne-Brighton Bus Lines, but in the late 1980s the routes were operated by the Metropolitan Transit Authority, initially from a depot in Elwood but later from Footscray and Sandringham.