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In 2018, a Metrodecker EV prototype from Optare was trialed on the route.
In November 2021, the frequency of the service was reduced from 6-8 minutes to 8-10 minutes. On 22 November 2021, Transport for London announced proposals to alter several routes. Part of this was to start route 21 at Nag's Head instead of Newington Green allowing the route to replace part of route 271, which would be withdrawn.
Incident
On 1 April 2017, a number 21 bus blocked the street in Cornhill as it became stuck after mounting the curb during an attempted three-point turn.