Boris Johnson suffered a substantial backbench rebellion as 35 Conservative MPs opposed the extension of coronavirus laws for a further six months.
The Prime Minister had ordered his MPs to support an extension to wide-ranging powers contained in the Coronavirus Act.
But several ignored this and opted to vote against, including former cabinet ministers David Davis and Esther McVey.
Conservative MP Chris Green (Bolton West) acted as a teller for the noes, also a sign of rebellion.
For Labour, 21 Labour MPs rebelled to oppose the extension – including former shadow chancellor John McDonnell and one-time leadership hopeful Rebecca Long-Bailey.
Health Secretary Matt Hancock explained some of the powers in the Act need to be renewed every six months, including measures to protect tenants and renters from eviction and to provide statutory sick pay to people throughout a period of self-isolation.
Parts of the legislation have been allowed to expire, but concerns were expressed about powers which could impede the right to protest.
The extension of measures in the Act was approved by 484 to 76, majority 408.
The division list showed 305 Conservative MPs and 176 Labour MPs were among those to support it.
A total of 10 Liberal Democrats voted against the extension, with former minister Alistair Carmichael also acting as a teller.
Seven DUP MPs, Alliance MP Stephen Farry (North Down), Green Party MP Caroline Lucas (Brighton Pavilion) and former Labour leader Jeremy Corbyn – currently sitting as an independent – also opposed the measures.
The 35 Conservative rebels were: Adam Afriyie (Windsor), Steve Baker (Wycombe), Harriett Baldwin (West Worcestershire), Bob Blackman (Harrow East), Peter Bone (Wellingborough), Graham Brady (Altrincham and Sale West), Christopher Chope (Christchurch), Geoffrey Clifton-Brown (The Cotswolds), Philip Davies (Shipley), David Davis (Haltemprice and Howden), Jonathan Djanogly (Huntingdon), Richard Drax (South Dorset), Mark Francois (Rayleigh and Wickford), Marcus Fysh (Yeovil), Mark Harper (Forest of Dean), Philip Hollobone (Kettering), David Jones (Clwyd West), Pauline Latham (Mid Derbyshire), Jonathan Lord (Woking), Tim Loughton (East Worthing and Shoreham), Craig Mackinlay (South Thanet), Karl McCartney (Lincoln), Stephen McPartland (Stevenage), Esther McVey (Tatton), Anne Marie Morris (Newton Abbot), John Redwood (Wokingham), Andrew Rosindell (Romford), Henry Smith (Crawley), Julian Sturdy (York Outer), Desmond Swayne (New Forest West), Robert Syms (Poole), Craig Tracey (North Warwickshire), Charles Walker (Broxbourne), David Warburton (Somerton and Frome), William Wragg (Hazel Grove).
The 21 Labour rebels were: Diane Abbott (Hackney North and Stoke Newington), Apsana Begum (Poplar and Limehouse), Ben Bradshaw (Exeter), Richard Burgon (Leeds East), Dawn Butler (Brent Central), Andrew Gwynne (Denton and Reddish), Ian Lavery (Wansbeck), Emma Lewell-Buck (South Shields), Clive Lewis (Norwich South), Rebecca Long-Bailey (Salford and Eccles), John McDonnell (Hayes and Harlington), Ian Mearns (Gateshead), Kate Osamor (Edmonton), Kate Osborne (Jarrow), Bell Ribeiro-Addy (Streatham), John Spellar (Warley), Graham Stringer (Blackley and Broughton), Zarah Sultana (Coventry South), Jon Trickett (Hemsworth), Derek Twigg (Halton), Beth Winter (Cynon Valley).