Plans for a line between Hitchin and Royston were placed before Parliament in 1846 by the Royston and Hitchin Railway company. The line was initially planned to be a single track spur from Hitchin, but during debate in the Lords it was recommended that the line be two track in the view of its possible later use as part of a route from to although this was later superseded by the Varsity line via. The line was opened in 1851 then extended to Cambridge although this was resisted by the company already operating a service from via the West Anglia Main Line. The line was then leased by the Great Northern in 1850 and subsequently purchased in 1898 and through services run from to. In 2002, a train travelling from King's Cross to King's Lynn, via Cambridge, crashed at Potter's Bar, shortly before set to join the Cambridge line, killing seven. As part of the Great Northern Route electrification by British Rail in the mid 1970s, the through service was severed by the need to change from the electrified service at to a diesel train stopping at all stations to. The extension of electrification through to Cambridge was completed in 1988 under Network SouthEast and the track improved to increase speed. Occasional services are run by 12-car trains allowing them to stop only at Royston & Letchworth Garden City where the platform is long enough to accommodate them. The platform extension at Letchworth Garden City was completed in December 2011. The Down platforms at Shepreth and Foxton were extended in 2017 to allow 8-car trains to stop without blocking the level crossings. The flat junction at has always been an issue with conflicting train movements, but the Hitchin flyover to the north of the existing junction was opened in 2013 to carry north-bound services over the East Coast Main Line.
Services
Services on the line are run by both Thameslink and Great Northern as part of their Great Northern Route. A mix of Express, Fast and Stopping services are provided on the line including services through Central London to and from Brighton. An alternative route via the West Anglia Main Line links to now provides mainly stopping services though some peak hour trains stop only at Tottenham Hale and Audley End.
Just under a mile to the east of Royston station lies the boundary between the Network RailLondon North Eastern Route and Anglia Route. All signals between King's Cross and this point are controlled by Kings Cross Power Signal Box, whilst those from here to are controlled by Cambridge Signal Box. The signalling system for the whole Cambridge line is Track Circuitblock, with all main signals being multiple-aspect colour light signals.
Stations
In order from southwest to north.
Passenger volume
These are the passenger usage statistics on the National Rail network from the year beginning April 2002 to the year beginning April 2010. Comparing both years, Cambridge has increased by nearly 51%, Foxton by 57%, Shepreth by 99%, Meldreth by 41% although it has declined in recent years until this point, Royston increased by 28%, Ashwell and Morden by 30%, Baldock by 50%, Letchworth Garden City by 33% and Hitchin by 44%.