Members of the Communication Workers Union (CWU) will begin strike action at 4pm this afternoon.
About 42,000 mail centre staff and drivers are expected to walk out ahead of 78,000 delivery and collection staff tomorrow over of a long-running dispute over pay, jobs and modernisation.
The Royal Mail and CWU had been locked in talks aimed at averting the national strikes but the two have so far failed to reach an agreement.
The strikes are expected to cause significant disruption to businesses in the run up to the busy Christmas period.
Research recently carried out by the Centre for Economics and Business Research for Kelkoo has estimated that a nationwide strike could cost UK businesses £1.5bn in lost revenues, with the cost to the retail sector about £270m.
Retailers including John Lewis, Amazon, eBay and Argos to discuss using alternative delivery services over fears that the strike will seriously disrupt business in the run-up to Christmas
Earlier this week, advertiser body ISBA warned if strike action went ahead companies could move their business away permanently and turn from direct mail to email.
Royal Mail plans to hire 30,000 temporary staff to clear the backlog caused by the strike and deal with the busy Christmas period.