David Beckham started on the bench, with in-form Aaron Lennon taking his place on the right of midfield; Steven Gerrard was pushed out to the left. Emile Heskey started up front with Wayne Rooney, whose temperament and professionalism has been called into question this week.
England removed their 'anthem jackets' to reveal new, plain retro-style kits prior to kick-off and the new-look Three Lions certainly roared out of the traps, threatening to overrun their 'rabbit in the headlight' like visitors.
Before seven minutes were on the clock, they had their opener. Wayne Rooney and Steven Gerrard linked up superbly on the left, with the former playing a lovely reverse pass and the latter taking it on the spin. Gerrard then turned it across the face of goal and Emile Heskey was able to bundle home his first ever Wembley goal.
A couple of minutes later, it should have been two. Rooney stroked a gentle cross – against from the left where most of the play was developing – but Heskey got far too much on his header, with the ball flying over. That was the forward's last practical involvement: he limped off to be replaced by Carlton Cole soon after.
The Fighting Jondas did eventually find their voice midway through the half, and enjoyed their first significant spells of possession. Stanislav Sestak slashed an effort wide, but at least he'd reminded the England rearguard that they were playing a football match.
Still, England continued to create half chances. Goalkeeper Stefan Senecky had to save Frank Lampard's volley after good work by Lennon, before Gareth Barry came close to connecting with Rooney's hanging cross at the back post.
Slovakia's best attempt came thereafter. Marek Cech's ball from the left found Miroslav Karhan, whose nonchalant side-footed effort forced a brilliant save from a flying David James.
Further disaster struck England's front-line on 34 minutes. Heskey's replacement Cole was also forced off after breaking down, with a half-fit Peter Crouch loping on.
Both teams managed to fashion a decent opportunity before the interval. Lampard's fine slide challenge released Lennon and the defence stood off the winger. He tried to beat the 'keeper at his near post, to no avail, and Gerrard couldn't do any better with the follow-up header.
At the other end, skipper Robert Vittek drew another good save from James after Matthew Upson's dreadful decision to let the ball run across him on the edge of his area.
Those who'd made it back to their seats hailed the introduction of David Beckham for the second period. With this 109th cap, he surpasses Bobby Moore's record haul for an outfield player.
The half took some time to get into full flow and, when it did, it was Vladimír Weiss' men who threatened. The Slovaks found too much space on the break and Erik Jendrisek eventually hit the side netting when he might have crossed.
Thereafter, England started to impose themselves as they had in the opening stages of the first half.
First, Fabio Capello's men had a 'goal' chopped off. Beckham's golden ball found the head of Crouch, whose effort looked to be bobbling into the net. Captain John Terry then decided to force it over the line, but he'd come from an offside position.
Almost immediately afterwards, Beckham found Rooney, but his touch wasn't deft enough and the ball was half-cleared. Terry then shot wide as he tried to make amends for his error.
However, the floodgates did eventually open with 20 minutes remaining. Beckham chipped in from the right and his delightful ball was powered into the net by the head of an unchallenged Rooney.
Crouch was then replaced by Michael Carrick, completing an incredible sequence of changes which could leave Capello struggling up front for next Wednesday's qualifier against the Ukraine.
Still, England pressed on and, following some good passing movement outside the visitors' box, they scored their 500th goal at Wembley. Carrick played in the onrushing Lampard, who finished across the 'keeper with a low drive into the far left corner after 82 minutes.
At the death, the Chelsea man turned provider for Rooney who, despite hints of offside, was allowed to finish coolly and high into the net, thus completing an eventual romp.
Greg Ptolomey, Goal.com