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Part of the Tonbridge Road in Barming will be closed from 7pm tonight so emergency repairs can be carried out.
The closure will be in place for the weekend so South East Water can fix a leaking pipe which is "undermining the road surface".
Although the road will be shut for normal traffic, emergency services and vital hospital deliveries will still have access.
Set to close between Halfpenny Close and Fountain Lane, it is expected to reopen on Monday at 6am.
A diversion route is signposted through the A20 at Leybourne, the A228 at Ashton Way, Malling Road to Mereworth Roundabout before re-joining the A26 (Tonbridge Road).
This section of Tonbridge Road is very near to the site of the notorious sink hole which swallowed up the tarmac in 2018. It took more than five months to reopen the road after the gaping hole appeared outside Barming Taj.
South East Water says this leak is unrelated but is "very aware of the previous issues" so wants to "fix the leak as quickly as possible to prevent any further problems."
The company has chosen to shut lanes in both directions as leaving just one lane open would make the road too tight for large lorries to navigate when turning.
When such hospital vehicles need to get through, workers will cover the road with boarding to let them pass. But this would not be feasible for all traffic.
Regional leakage manager Greg Groombridge said: "We’re very sorry for the inconvenience caused to motorists by the burst and subsequent road closure this weekend.
"Due to the complex location of the burst we need to close the road for the safety of the road users and our staff repairing the leak.
"We are completing this emergency repair this weekend to prevent any further damage to the road surface, which could result in a longer closure if not repaired now."
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