The London and Birmingham Railway, now part of the "West Coast Main Line", was officially opened from Euston as far as Denbigh Hall (approximately one mile north of Bletchley station) on 9 April 1838, where a temporary station was built. The line was fully opened in September 1838, and Bletchley station opened some time between 2 November 1838 and 20 June 1839.

 The station was known as Bletchley & Fenny Stratford between 1841 and 1846 and after the opening of the Marston Vale line was referred to in timetables as Bletchley Junction from 1851 to 1870. Originally a major intercity station, that role passed to Milton Keynes Central in 1982 when the latter was opened, long after the east–west route had been downgraded, taking Bletchley's importance as a junction with it.

The eastward route (to Bedford St Johns) opened in 1846. The westward route (to Buckingham) opened in 1850. This east–west route subsequently became the Oxford – Cambridge "Varsity Line".The London and Birmingham Railway, now part of the "West Coast Main Line", was officially opened from Euston as far as Denbigh Hall (approximately one mile north of Bletchley station) on 9 April 1838, where a temporary station was built. The line was fully opened in September 1838, and Bletchley station opened some time between 2 November 1838 and 20 June 1839.