The Silvertown Tunnel will close for 17 nights through to the end of June for maintenance work — less than two months after opening.
General maintenance and snagging works will take place in the tunnel on several dates between now and June 22, Transport for London has said.
During the southbound only closures, buses will be diverted via the Blackwall Tunnel.
When the northbound or both directions are closed, buses will operate a split-service terminating at Canning Town and North Greenwich.
Customers will be advised to use alternative routes, like the Tube or take the route 108, to complete their journeys across the river.
A TfL spokesperson said: "TfL will look to ensure bus services can continue to run where possible and has been communicating with drivers about the closures and weekly customer emails."
The Silvertown Tunnel, which opened on April 7, cost around £2.2 billion and was created with the aim of reducing northbound delays through the Blackwall Tunnel.
It stretches almost a mile (1.4km) under the River Thames from Greenwich to Newham, next to the Blackwall Tunnel. Both tunnels are subject to tolls and cost £4 during peak times.
The absence of dedicated cycling lanes led to protests, including a mass trespass by approximately 1,000 cyclists on April 25, temporarily halting traffic through The Silvertown Tunnel.
Full list of the planned overnight closures: