Parts of the route are currently incomplete and some sections follow other routes.
The proposed route is to begin in central London, running from Charing Cross via Paddington railway station to the Grand Union Canal. The towpath alongside the canal between Paddington and Northolt is already designated as a local cycle path, and will eventually form part of Route 6 when the route is completed. The canal continues to Uxbridge where the National Cycle Route 6 joins National Cycle Route 61 at Cowley, near Brunel University, sharing the same path until the two routes diverge at St Albans. The route continues along the Grand Union Canal and the Colne Valley on mainly traffic-free routes. At Rickmansworth it joins the Ebury Way, a rail trail which runs along a former line of the Watford and Rickmansworth Railway. Entering central Watford, the route continues north via St Albans with some on-road sections to Harpenden, where it intersects with National Cycle Route 57 and the Chiltern Cycleway. It then progresses along the River Lea via Luton, along the Sewell Greenway before joining the road network to reach Leighton Buzzard. At this point is re-joins the Grand Union Canal (Grand Junction Branch) to reach Bletchley, and then continues on mostly traffic-free paths to Milton Keynes.
Route 6 enters Milton Keynes from the south following the Grand Union Canal in southern Bletchley. After a loop through central Bletchley close to Bletchley railway station and Bletchley Park, it resumes its track northwards via Fenny Stratford along the valley of the River Ouzel (near The Open University and the Milton Keynes University Hospital) to Campbell Park (where it intersects National Cycle Route 51 heading west to Central Milton Keynes and Milton Keynes Central railway station). At Great Linford, NCR6 heads west along the former Wolverton to Newport Pagnell Line (now a rail trail). At Old Wolverton (near Wolverton railway station), the route crosses the River Great Ouse to leave the Milton Keynes Urban Area for the rural villages of Castlethorpe and Hanslope before crossing into Northamptonshire.
Route 6 between Milton Keynes and Derby is the core section of the Sustrans route of the South Midlands. After passing through Northampton the route follows the Brampton Valley Way for 14 miles (23 km) to Market Harborough, first opened in 1993 it is one of the longest railway paths in the country and uses two long tunnels. From Market Harborough the route uses the towpath of the Grand Union Canal to reach Foxton Locks from where it is on street to south Leicester. Using the River Soar towpath the route passes south to north through the city. On reaching Watermead Country Park the route returns to the streets to pass through Loughborough and on to Worthington. From here the 13 miles (21 km) to Derby follow the Cloud Trail and Derby Canal Path.
From Derby the route heads east through Long Eaton and then turns north in the western suburbs of Nottingham. Passing Beeston, Bulwell, Hucknall and Newstead railway stations before heading northeast through the grounds of Newstead Abbey. From Blidworth the route is northbound and predominantly traffic free as far as Worksop as it passes through Sherwood Pines Forest Park, Sherwood Forest Country Park and Clumber Park. Using the canal towpath between Worksop and Shirebrook the route heads east on country roads to the Rother Valley Country Park. Here it turns north to Rotherham, from where it becomes traffic free joining a towpath for a southwesterly route to Sheffield. Climbing through the streets of Sheffield the route enters the Peak District National Park at Ringinglow and uses the dam wall of Ladybower reservoir to reach Castleton.
The route between Caslteton as Reddish has yet to be decided.
From Reddish, National Route 6 enters Manchester via the Fallowfield Loop. Passing through Whalley Range and Manchester city centre it then follows part of the Irwell Sculpture Trail as it runs through Drinkwater Park and north towards Bury.
Route 6 meets the following routes:
Route 6 between Derby and Sheffield is part of the Derby to York cycle route along with: