Harry Ellis scored twice on his return after a six-week absence, wing Tom Varndell also added two, Jordan Crane scored another and replacement Matt Smith grabbed a score on his Saxons debut.
Saracens centre Adam Powell (2), clubmate Noah Cato and Wasps centre Dom Waldouck were3 the other try-scorers on the night.
After almost opening the scoring from the kick off, the Saxons struggled to break through a determined Portuguese defence, despite dominating the opening exchanges.
But their break came at the end of the first quarter as Ellis dived over from the base of a scrum. Bristol fly-half Ed Barnes celebrated his debut with the first of four conversions to take the score to 7-0.
Minutes later, Powell scored his first and Barnes added the extras.
On the half-hour, Nick Abendanon's cross-field kick and a kind bounce allowed Varndell to touch down on the left and with Portugal captain Joao Correia in the sin bin, Ellis added a second in similar fashion to his first.
Cato finished off an excellent effort involving forwards and backs, and Barnes' conversions took England's half-time lead to 33-0.
It was 15 minutes in to the second half before England added to that, Waldouck scoring a try which Alex Goode converted.
With a 40-point cushion, a flurry of substitutions followed and it was Waldouck's replacement, Leicester’s Matt Smith who was next to touch down, finding the try line with his first touch of the ball.
As the game neared its conclusion there were further tries for Varndell and his Leicester team-mate Crane, playing at second row for the first time since representing England Under-18s, before Goode converted Powell's second try which took the final score to 66-0.
Head coach Stuart Lancaster said: "We played some really good rugby and I'm delighted for the boys. Portugal put a lot of pressure on us in the opening stages but when we adjusted and got some depth, things started to come and we scored some great individual tries."
The England Saxons squad to face Ireland A at Donnybrook next Friday will be named on Monday.
England Saxons: Nick Abendanon (Bath Rugby)*, Tom Varndell (Leicester Tigers)*, Dominic Waldouck (London Wasps), Adam Powell (Saracens), Noah Cato (Saracens), Ed Barnes (Bristol Rugby), Harry Ellis (Leicester Tigers)*, Dan Cole (Leicester Tigers), Rob Webber (London Wasps), Dave Wilson (Newcastle Falcons), Jordan Crane (Leicester Tigers)*, George Skivington (London Wasps), Kearnan Myall (Leeds Carnegie), Andy Saull (Saracens), Phil Dowson (Newcastle Falcons, captain)
Replacements: 16. Joe Ward (London Wasps) for Webber 49, 17. Nathan Catt (Bath Rugby) for Cole 55mins, 18. Tom Mercey (Saracens) for Wilson 61 mins, 19. Jon Fisher (London Irish) for Saull 69 mins, 20. Joe Simpson (London Wasps) for Ellis 61 mins, 21. Alex Goode (Saracens) for Barnes 49, 22. Matt Smith (Leicester Tigers) for Waldouck 55 mins
Scorers: Tries: Ellis 2, Powell 2, Varndell 2, Cato, Waldouck, Smith, Crane Pens: Cons: Barnes 4, Goode 4
Portugal: Pedro Cabral, Aderito Esteves, Diogo (David) Mateus, Franciso Mira, Gonçalo Foro, Duarte C.Pinto, José Pinto, Jorge Segurado, João Correia, Juan Murré, Juan Severino, Gonçalo Uva, Eduardo Acosta, Salvador Palha, Vasco Uva
Replacements: 16. João Junior for Correia 32-41 mins and for Segurado 53mins, 17. Nuno Taful for Palha 32-41mins and for Correia 75, 18. David dos Reis for Uva 16mins, 19. Antonio Duarte for Severino 61 mins, 20. Pedro Leal for Pinto 53mins, 21 Pedro Silva for Esteves 24mins, 22. Antonio Aguiilar for Mira 45mins
Sin binned: Correia (31-41)
Referee: P Allan (Scotland)