Unite the Union will open the ballot to more than 3,000 bus drivers and over 250 office staff in a row over pay.
If the workers vote in favour of strikes, which would cause widespread disruption in the region, they will join around 200 National Express engineers who are also ready to take industrial action following a successful strike ballot.
Union bosses said National Express reported huge profits in 2021, but has offered all of its workers in the West Midlands a "real terms pay cut".
Some drivers earn as little as £11.80 per hour, while the majority of admin staff make little more than the minimum wage, Unite said.
Unite general secretary Sharon Graham said: “National Express brings in huge amounts of money while its workers are struggling with the cost-of-living crisis.
"It can afford to pay for a decent wage for its workers and that is exactly what it needs to do.
“Unite defends our members' jobs, pay and conditions to the hilt and National Express West Midlands’ workforce have the union’s complete support as they fight for a fair pay rise.”
The union says that although National Express claims it has offered drivers a 14 per cent rise, it is worth just eight per cent – which is below the rate of inflation.
Bosses said admin staff have been offered nothing at all and the engineers have been offered 10 per cent.
The ballot for strike action opens on February 8 and closes on March 1, with strikes likely to begin later that month if workers vote in favour.
Unite regional officer Sulinder Singh said: “The disruption to passengers across the region would be immense and entirely the fault of National Express’ greed.
"It needs to put forward a pay rise our members can accept – it certainly has the resources to do so.”
National Express West Midlands said engineers had been offered between a 10.5 per cent and 13.2 per cent increase, and it had agreed with Unite to delay the talks about admin staff until the drivers and engineers talks had been resolved.
A spokesperson for National Express West Midlands said: “We have offered our drivers an increase of the average rate by 14 per cent - this is made up of around six per cent provided already in November 2022 and eight per cent additional that we would backdate to January 2023.
"Under this deal, around 75 per cent of drivers would earn more than £30,000 and we have promised no compulsory redundancies if they accept this offer.
“This is a fair and responsible offer. It is fair because it acknowledges that times are tough for everyone and it is responsible because it safeguards the long term interests of the communities we serve.
"We encourage our colleagues to vote to reject industrial action and keep the West Midlands moving.”