But flanker Lewis Moody was sent off for fighting near the end, with Samoan wing Alesana Tuilagi - his Leicester team-mate - also dismissed following a tackle on Mark Cueto which sparked a mass brawl.
Moody was the first England player red-carded in a Test match at Twickenham.
Fly-half Charlie Hodgson steered the world champions past spirited but limited opponents, amassing 20 points through a try, three penalties and three conversions.
And Wasps wing Tom Voyce marked his first Twickenham start in England colours by claiming a try double as Samoa inevitably folded under relentless pressure from a heavyweight home pack.
Scrum-half Harry Ellis, an impressive alternative to World Cup winner Matt Dawson, also added a touchdown, while replacement Tom Varndell scored the final try with England scoring 24 unanswered second-half points.
It concluded a satisfactory November programme for England, who claimed Samoa's scalp two weeks after beating Australia and seven days on from a four-point defeat against New Zealand.
The victory surpassed England's previous best winning margin of 22 points against Samoa during World Cup 1995, and sends them into their Six Nations opener against Wales on February 4 with spirits high.
However, they still have a lot of work ahead to address their often sloppy back play, and the loss of an injured James Simpson-Daniel at half-time meant the Gloucester speedster was never seen in full flight.
England's forwards dominated, despite losing injured prop Andrew Sheridan midway through the first period, while Perry Freshwater, Lee Mears and Varndell all made their Test debuts off the replacements' bench.
Samoa's best attacking moments came early on, but they were reduced to 13 men at one stage of the second half when prop Justin Va'a and then fly-half Tanner Vili - for a reckless high tackle on Cueto - were sin-binned in quick succession.