David Frost resigned "with immediate effect" after telling Prime Minister Boris Johnson that establishing a new relationship with the EU would be a "long-term task."
Frost, who has overseen the EU discussions, is claimed to have handed in his resignation letter to Johnson last week, along with an agreement to leave in January.
According to the Mail on Sunday, Frost's decision was triggered by the execution of Plan B coronavirus safeguards, including the use of COVID-19 passes.
In a letter to the prime minister posted Saturday evening, he stated that he was "disappointed that this plan has become public this evening and in the circumstances, I think it is right for me to write to step down with immediate effect."
Frost expressed gratitude to Johnson and stated that "Brexit is now secure," but added that "The challenge for the Government now is to deliver on the opportunities it gives us."
"You know my concerns about the current direction of travel," Frost continued.
He also expressed regret that the removal of COVID-19 restrictions had not proven "irreversible" as promised, adding, "I hope we can get back on track soon and not be tempted by the kind of coercive measures we have seen elsewhere."
Johnson said he was "very sorry" to have received Frost's resignation.
Frost had lately been embroiled in contentious rounds of negotiations with European Commission Vice-President Maros Sefcovic as the UK and EU attempted to close gaps in post-Brexit arrangements.