As of 2014, according to Stagecoach East's Managing Director, Andy Campbell, the route carries on average 1.3 million passengers annually.

[2]) From 1851 to 1967, there was a direct rail service from Oxford to Cambridge with travel time about two hours, known as the Varsity Line.

In response to the lack of rail service, route X5 was launched in September 1995 with travel time between the two locations taking about 3.5 hours.

Buses operated hourly and provided a number of new links between towns which had not previously been connected by bus or rail services.

The western part of the route replaced an infrequent Stagecoach United Counties service between Oxford and Bedford.

[4][5] The route remained largely unchanged until August 2004, when it was diverted via Roxton and Wyboston to replace withdrawn local services.

[3] Early in 2005 the X5 was doubled in frequency to operate half-hourly and rebranded as Cross County, a name also used for the (then) X4 service between Milton Keynes and Peterborough.

[3][5] In 2006 the route briefly faced competition in the form of an air service between the two termini operated by Sky Commuter.

[4] The service was slightly rerouted in August 2011 to serve the town centre in Buckingham instead of stopping at the more remote Tesco superstore.

[16] The X5/905 connects Oxford and Cambridge via Bicester, Buckingham, Milton Keynes, Bedford (where through passengers have to change to the 905) and St Neots.

[5][21][22] These were replaced by higher capacity Alexander Dennis Enviro400 MMC double deck buses in 2021 as noted previously.