On 10 November 2007 the route was extended from Euston to King's Cross. The move, which was intended to provide a direct link between Waterloo and St Pancras stations, coincided with the relocation of the Eurostar terminal.
On 29 June 2019, the route was withdrawn from Euston and Kings Cross King's Cross.  On the front of the buses, and on the iBus, it is announced as terminating at Russell Square, and sometimes Euston
In 2007, the route was used by two residents of Brixton as the starting point for a journey around the world using any method of transport except the aeroplane.
On 20 December 2013, thirty people were injured when the driver of a route 59 bus (a DAF DB250LF with Wright Pulsar Gemini body, fleet number DW84 and registered as LJ04LFX) swerved to avoid a vehicle and hit a tree in Kennington. Seven people were seriously injured.
Route 59 operates via these primary locations:
- Streatham Hill Telford Avenue
- Brixton station
- Kennington for Oval station
- Lambeth North station
- Waterloo station
- South Bank
- Waterloo Bridge
- Holborn station
- Russel Square
- Euston bus station for Euston station
- "Arriva London's route 59 converts to New Routemasters". Arriva London. 23 March 2016.
- Route 59 (third) Archived 14 May 2008 at the Wayback Machine busesatwork.co.uk
- Route 59 extended to St Pancras and King's Cross Transport for London 30 October 2007
- "Around the world in anything but a plane". Daily Mail. 5 March 2007. Retrieved 21 January 2014.
- Kerr, Sarah (20 December 2013). "At least 20 injured, two critical, after south London bus crashes into tree". Metro. Retrieved 20 December 2013.
- "London Bus Crash Leaves 32 Passengers Injured". Sky News. 20 December 2013. Retrieved 20 December 2013.
- Saul, Heather (20 December 2013). "Kennington bus crash: 32 injured after double decker hits tree in south London". Independent. Retrieved 20 December 2013.
- Prynne, Miranda; Payton, Matthew (20 December 2013). "Seven people seriously injured and 25 others hurt in Kennington Road bus crash". The Daily Telegraph. Retrieved 20 December 2013.
- "London bus crash: Seven people seriously injured". BBC News. 20 December 2013. Retrieved 20 December 2013.
- Route 59 Map Transport for London