The measures - including ordering people to work from home, to wear masks in public places and use COVID-19 passes to enter some venues - are expected to be approved by parliament but with Johnson relying on the opposition Labour Party for votes.
It's yet another blow to a prime minister already under pressure over reported parties in his Downing Street office last year when such gatherings were banned, a pricey refurbishment of his apartment and the chaotic withdrawal from Afghanistan.
Many of his MPs say the restrictions are draconian, with several questioning the introduction of vaccination certification, dubbed COVID-19 passports, to enter some venues such as night clubs.
Others are using the votes as an opportunity to vent their anger at Johnson, believing the man who helped the Conservatives win a large majority at a 2019 election is squandering the party's successes by self-inflicted missteps and gaffes.
But despite the grumblings of discontent, Conservative Party insiders say there is not enough of a groundswell against Johnson to dislodge him yet, with no potential challenger commanding enough support to replace him.
"Boris on a bad day is better than any of the other wannabes on a good day," one veteran Conservative said.
Before the series of votes on the measures, due to start at about 6.30pm, Johnson warned his cabinet of top ministers that there was a "huge spike" in Omicron cases heading the UK's way and that the measures were necessary to protect people.
"The PM (prime minister) said a huge spike of Omicron was coming and the measures we aim to introduce as part of plan B were balanced and proportionate, helping to reduce transmission while we ramp up the booster program," his spokesman said.
The UK has registered almost 4500 cases of Omicron, with 10 people hospitalised.
Johnson said on Monday that one person had died after contracting the variant.
Ministers are moving to try to win over the Conservative rebels, saying that people who have not been double-jabbed can instead offer proof of a negative lateral flow test to gain access to indoor venues of more than 500 people.
But several are not convinced, with one, Andrew Bridgen, saying some MPs were determined to "draw a line in the sand with regard to any further erosion of civil liberties and freedoms".
Conservative former minister David Johnson described the move to introduce COVID-19 passes as "quite wrong".
"People should certainly be encouraged to have the vaccine... but ultimately people have to take responsibility for their own health," he told Reuters.
