"With great regret, I'm resigning from the Government," Johnson, who also serves as minister for London, tweeted.
In a statement, Johnson said the proposed Brexit plan would leave the country economically weakened, while a no-deal would "inflict untold damage" on the nation.
"Brexit has divided the country. It has divided political parties. And it has divided families too. Although I voted Remain, I have desperately wanted the Government, in which I have been proud to serve, to make a success of Brexit: to reunite our country, our party and, yes, my family too," Johnson wrote in his resignation statement.
Theresa May's government is trying to settle the remaining five percent of the deal to trigger a deal-making summit later this month. According to the prime minister, despite the fact that 95% of the Brexit withdrawal agreement has been done, the UK government is still facing the challenge of resolving the Irish backstop issue.
The European Union and the United Kingdom have less than six months to reach an agreement on Brexit before the UK leaves the bloc. The present differences create a risk of a no-deal scenario following the March 29, 2019 deadline.