Further tries from Ben Morgan and Anthony Allen, plus a final minute penalty try, as well as 17 points from the boot of Charlie Hodgson saw England wrap-up victory.
But sloppy defending saw the tourists concede four tries of their own, two to Shaun Venter and one apiece to Joubert Engelbrecht and Deon Scholtz, while full-back JC Roos kicked 11 points.
The match will also add to the injury worries of England coach Stuart Lancaster as Ugo Monye was stretchered from the field early in the clash, having taken a knock to the head after an unsuccessful tackle on Venter.
Monye lost consciousness after hitting his head on the lower back of Venter before his head also made contact with the ground. But the Harlequins player was conscious before he was replaced and was said to be walking around the changing room shortly after.
Former Super 15 Bulls player Roos got the match off to a positive start for the hosts when he landed a spectacular penalty from the half-way line.
But this was almost immediately cancelled out by Hodgson as the SA Barbarians were penalised from the re-start for failing to release the ball after collecting the kick.
Things continued to be cagey for the first 15 minutes before a flurry of activity saw both sides cross over the try-line.
First, Nicky Steyn created a piece of magic for the hosts, the number eight breaking from the half-way line before offloading to Engelbrecht, who evaded the attempted ankle tap-tackle of Abendanon to run the try in.
Roos added the conversion but the lead was short-lived for the SA Barbarians as Lee Dickson found Christian Wade on the left, the winger drawing the defence with him before passing to Abendanon for the easy run in.
Hodgson again added the extras before the floodgates opened for England.
Morgan got in on the act as England made good on 10 solid minutes of pressure inside their opponents 22, the number eight taking the ball off Jordan Turner-Hall and diving over the line.
Hodgson, who only missed one kick all night, was on hand to maximise the score before the injury to Monye caused a five-minute delay in proceedings.
When things did eventually get back underway, England wasted little time in re-establishing their dominance.
Wade was unlucky not to get on the scoreboard when only a shoulder barge from Scholtz denied him a try in the left corner. Instead the ball went back for a five metre scrum and it was Abendanon who eventually crossed over, the ball having passed through almost every English hand on the pitch.
Abendanon wrapped up his hat-trick five minutes later when Monye’s replacement May punted a loose ball upfield before setting off at an electric pace in pursuit. The winger was unlucky not to get the bounce and complete the score himself but Abendanon was on hand to dive on the ball ahead of Scholtz and ensure the half ended on a high for the tourists.
The second half was incredibly scrappy from England as the South Africans pegged them back with a pair of tries from Venter. The first came when the fly-half ducked through a gaping hole in the English defence, while his second was a classic example of exploiting a one-man overlap after England had seen Jamie Gibson sent to the sin-bin for a tackle off the ball.
It took a moment of inspiration from May to get England back on track, the substitute shaking off one tackle, dancing 180 degrees through a second and forcing his way through a third to skip over the line for his first try.
Although Hodgson failed to add the conversion this time, it was enough to help England steady the ship, May grabbing his second 10 minutes later after finding himself in the perfect position to collect and dart over the line after first Abendanon and then George Robson had pulled up just short.
Replacement Allen got his name on the on the scoreboard two minutes later, picking the ball up off his bootlaces after a pass from Karl Dickson; Hodgson brought up the half-century of points with his conversion.
The South African Barbarians appeared to have ended things on a high for home fans, Scholtz breaking away for a solo try before Roos maximised the score.
But a penalty try in the final minute, when the South African team were penalised for deliberately collapsing the maul just centimetres short of the line, sugar-coated things for England with Hodgson adding another conversion with the final kick of the half.
England take on South Africa in Port Elizabeth in the third and final Test on Saturday, looking to avoid a series whitewash after losing the opening two matches in Durban and Johannesburg.