Forty-four Tory MPs have rebelled against the government, on a vote on regulations linked to the 10pm curfew for pubs and restaurants in England.
But they did not inflict a defeat on Boris Johnson, with most Labour MPs abstaining in the vote.
Several Conservative MPs spoke out against the three-tier restrictions scheme announced this week, but the House of Commons backed them.
Health Secretary Matt Hancock said they were needed to help save lives.
A group of backbench Conservatives forced a vote on a motion that could have gone through on the nod to register their disapproval over the curfew affecting pubs and restaurants in England.
The vote was symbolic as the new alert system coming into force includes the curfew.
Some 23 Labour MPs – including former leader Jeremy Corbyn – also voted against the government.
Ten Liberal Democrat MPs, six DUP MPs and the only Green MP, Caroline Lucas, joined them.
But they lost by 299 votes to 82 – a majority of 217.
During the debate, Mr Hancock said the curfew was a “matter of policy choice”, needed to restrict the number of cases and to keep schools and workplaces open.
He added that there was “direct and approximate evidence” of it having a positive impact, citing a fall in alcohol-related A&E admissions late at night.
Since pubs and restaurants have been forced to close earlier, many Tory backbenchers have queried whether the move is proportionate and whether it could lead to an increase antisocial behaviour, particularly with shops selling alcohol remaining open later.
One Tory MP, Craig Mackinlay, argued that the curfew could actually harm public health.
He said: “Just considering this great city of London, the restaurants are closed, the pubs closed, there is no takeaway available at 10 o’clock and, guess what, the first train out of London, or the next Tube at 10 past 10, is going to be rocka-chocka solid, [with people] mixing and mingling… at close proximity.”
In other developments on Tuesday, Labour leader Sir Keir Starmer called for a two-to-three-week “circuit-breaker”, involving tougher restrictions in England to cut the spread of coronavirus.
And Conservative MP for Bolton West, Chris Green, resigned as a junior member of the government, warning of the prime minister’s new restrictions system for England, that the “attempted cure is worse than the disease”.
They will come into force on Wednesday, with areas divided into three “tiers”, applying different levels of restrictions depending on the rate of infection.
Last week, 14 Tory MPs rebelled over the ban on gatherings of more than six people in England.
The 42 Conservative MPs who voted against the government were:
There were also two tellers: Philip Hollobone and Craig Mackinlay