Oxford Street and Bond Street will both be marking the start of the festive season as their lights are turned on at 5pm.
Roads between Portman Street and Oxford Circus were shut in the eastbound direction from 10am on Tuesday, while the Christmas lights are being installed.
Motorists have been warned that the route will be fully closed from 4pm to 8pm.
TfL tweeted: "Oxford Street Christmas Lights Switch-On - closures between Portman St & Oxford Circus from 10am (E/B only). Fully closed 4pm-8pm."
A TfL spokesman said: "While the road is run by Westminster council, we are also advising customers to plan ahead and to check TfL traffic and bus alerts to avoid delays to their journeys."
Oxford Street's switch-on is hosted by Capital FM and the NSPCC - and with "big artists" lined-up to perform, it is expected to draw large crowds.
A Westminster council spokesman said: "Oxford Street will be closed in stages, starting at 4pm.
"Shops in the area will close at 4.15pm, ahead of the crowds arriving, and reopen at 7pm after the light switch.
"The area will be busy so we recommend people plan their journey in advance."
You can check TfL for travel updates here .
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