The workers' first strike since 2008 comes as the plane maker is under heavy scrutiny from US regulators and customers after a door panel blew off a 737 MAX jet midair in January.
The mounting crises battered Boeing's stock and sparked a leadership upheaval. Boeing shares fell 3.4 per cent in US pre-market trading on Friday.
New CEO Kelly Ortberg CEO Kelly Ortberg has to confront a labour-management battle just weeks after he was brought in to restore faith in the company.
He proposed a deal including a pay rise of 25 per cent over four years, far lower than the 40 per cent workers had demanded.
Roughly 30,000 International Association of Machinists and Aerospace Workers (IAM) members who produce Boeing's 737 MAX and other jets in the Seattle and Portland areas voted on their first full contract in 16 years, with 96 per cent rejecting it and favouring a strike in a two-part ballot.
"This is about respect, this is about addressing the past, and this is about fighting for our future," said Jon Holden, who headed the negotiations for Boeing's largest union, before announcing the vote result on Thursday evening.
"We strike at midnight," said the union leader who had agreed to the just-defeated deal, as members in the union hall cheered and chanted: "Strike! Strike! Strike!"
A long strike could badly hit Boeing's finances, which are already groaning due to a $US60 billion ($A89 billion) debt pile.
Boeing said late on Thursday the vote sent a clear message that the tentative deal it reached with IAM leadership was not acceptable to members.
"We remain committed to resetting our relationship with our employees and the union, and we are ready to get back to the table to reach a new agreement," the plane maker said.
Although IAM leadership recommended last Sunday that its members accept the contract, many workers had responded angrily, arguing for the original demand and lamenting the loss of an annual bonus.
A strike presents Boeing with multiple challenges: it will need to decide how to respond at the bargaining table, after saying it had offered everything it could. It also must find a way to secure factories full of valuable, partially built planes without union workers to do the job.
Workers have been protesting all week in Boeing factories in the Seattle area that assemble Boeing's MAX, 777 and 767 jets.
If prolonged, a strike would also weigh on airlines that depend on the plane maker's jets and suppliers who manufacture parts and components for its aircraft.
The Boeing workers' last strike in 2008 shuttered plants for 52 days and hit revenue by an estimated $US100 million a day.
