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Route 135 commenced operating on 24 May 2008 between Cubitt Town and Moorfields Eye Hospital. It was initially operated at a frequency of every 15 minutes off-peak and every 10 minutes during peak hours, with a maximum requirement of 13 double-deck buses. The initial contract to operate the route was awarded to Arriva London's Barking garage. The route was featured in Time Out magazine in 2009.
The route number 135 has previously been used twice; for a service between Forty Hill and Brimsdown, until September 1982, and from November 1987 for a service between Marble Arch and Archway via Camden Town. The second service was operated by Metroline after privatisation, and was withdrawn in December 2000, being replaced by extending route 88 to cover part of its route and increasing the frequency of route 134, which already ran over much of the 135 route.