Announcing his departure on Twitter, the South Staffordshire MP said it had been a pleasure to serve in the role and that he was proud of the "transformational reforms" he had led in post-16 education.
Mr Williamson became Education Secretary in July 2019, having previously served as Chief Whip and Defence Secretary.
His replacement has been confirmed as Nadhim Zahawi, who moves across from his role as Vaccines Minister.
He had widely been expected to be one of the key departures in Mr Johnson's reshuffle, having been widely criticised for his handling of schools and exams during the pandemic.
Mr Williamson said: "It has been a privilege to serve as Education Secretary since 2019.
"Despite the challenges of the global pandemic, I’m particularly proud of the transformational reforms I’ve led in Post-16 education: in further education colleges, our Skills agenda, apprenticeships and more.
"This programme will create better life opportunities for pupils and students for many years to come. I look forward to continuing to support the Prime Minster and the government."
During his tenure as Education Secretary the South Staffordshire MP faced repeated calls to resign.
In the summer of 2020 the A-level and GCSE results row led to the Government being forced into a U-turn following protests over the downgrading of thousands of results.
Mr Williamson also received criticism over the recovery plan to help pupils catch up and confusion around children returning to class amid Covid-19.
In December, heads and unions were not happy when Mr Williamson threatened legal action against Greenwich council if it failed to keep its schools open to all pupils until the end of term, despite a rise in cases.
Weeks later, the Government announced national school closures.
Mr Williamson also faced calls to step down amid criticism of inadequate free school meal provision for pupils, and again after the schools catch-up tsar resigned over the Government’s £1.4 billion education recovery fund.
Last week he was also ridiculed after he said he had met footballer Marcus Rashford online, when he had instead talked to rugby player Maro Itoje.
Mr Williamson's departure was followed shortly afterwards by Robert Buckland and Robert Jenrick as Justice Secretary and Housing Secretary respectively, while Dominic Raab was demoted from Foreign Secretary to Justice Secretary, replacing Mr Buckland.
After receiving the axe, Wolverhampton-born Mr Jenrick pledged to continue supporting the Prime Minister “in every way I can”.
“I’m deeply proud of all we achieved,” he said, thanking his colleagues at the Ministry of Housing, Communities and Local Government.
His sacking from Mr Johnson’s top team followed controversies including the unlawful approval of a Tory donor’s housing development and his eyebrow-raising journeys during lockdown.
Also to go was Mr Buckland, who said it had been an “honour” to serve in the Government for the last seven years, including the last two as justice secretary and lord chancellor.
“I am deeply proud of everything I have achieved. On to the next adventure,” he said.
The courts system has been under huge strain during the pandemic, but a specific reason for his departure was unclear.
Confirmation that a reshuffle was being carried out came as Mr Johnson led Prime Minister’s Questions in the Commons.
“The PM will today conduct a reshuffle to put in place a strong and united team to build back better from the pandemic,” a No 10 source said.
“The PM will be appointing ministers this afternoon with a focus on uniting and levelling up the whole country.”
Mr Johnson’s presence in the Commons allowed him to sack ministers in his private office, away from the cameras in Downing Street.
Following Prime Minister’s Questions, Tory Party co-chairwoman and Cannock Chase MP Amanda Milling was also seen going into Mr Johnson’s parliamentary office.