Part of the Blackwall Tunnel is to shut this month as work continues on a new £2.2bn road tunnel linking east London with the Greenwich Peninsula.
Due to open in 2025, the 1.4km (0.9 mile) river crossing will link Silvertown, in Newham, with the peninsula in south-east London.
Work to complete the final road layout will see the southbound route of the Blackwall Tunnel close on 20-22 July and again on 17-19 August.
The northbound route of the tunnel will remain open, Transport for London (TfL) has said.
During the closures drivers are advised to plan a different route in advance.
The 108 bus, the only one that operates through the Blackwall Tunnel, will be split in two, running between Lewisham and North Greenwich, and between Canning Town and Stratford.
Passengers who complete their journeys using the Jubilee line will automatically be refunded.
They will not be charged for further bus journeys on the other side of the river, as long as they begin within an hour of getting on the first bus.
The closures will start at 00:01 BST on each Saturday, with southbound traffic restored by 05:00 each Monday at the latest.
The closures are the latest in a series, with the last ones taking place in June.
TfL’s director of capital delivery, Nick Fairholme, said: “We are now in the final phase of works to complete the Silvertown Tunnel, and these closures will help us to start to get the tunnel ready to open.
“We appreciate that these planned weekend works will have an impact on some drivers and are doing everything we can to limit potential disruption, including ensuring a northbound route through the Blackwall Tunnel is maintained throughout.”