The Gloucester wing, making his first Test start at Twickenham, was joined on the scoresheet by Ugo Monye, flanker Tom Johnson and centre Manu Tuilagi, who touched down twice late on against the tiring Fijians.
England's pack was so superior they struggled to retain control at times but their power did earn a penalty try while Fiji's captain and tight-head prop Deacon Manu was watching from the sin-bin.
England had talked about imposing themselves from the outset, about being ruthless and showing no mercy on Fiji as they prepare to face Australia, South Africa and world champions New Zealand.
Head coach Stuart Lancaster will be satisfied with the seven-try performance, disappointed by the two tries England conceded and aware they will need to be more accurate when the Wallabies come to town next Saturday.
England must retain their fourth place ranking through this most challenging autumn campaign to be among the top seeds when the 2015 World Cup draw is made on December 3.
England paid the price for starting slowly on their summer tour of South Africa and a more clinical team would have punished them in the first 20 minutes today.
Fiji bossed the opening quarter, with the powerful Gloucester number eight Akapusi Qera causing England all sorts of problems around the fringes.
England fell foul of referee Glen Jackson, the former Saracens fly-half, and had Danny Care sin-binned for what was considered to be a dangerous tackle.
It looked harsh but no one could have denied that Fiji deserved the lead they would have had if fly-half Metuisela Talebula had not dropped two penalty kicks woefully short.
In the end, England negotiated Care's absence and then turned the tables on Fiji, with man of the match Alex Goode particularly impressive in his role as the second play-maker.
After Flood had kicked England into the lead, the men in white attacked in waves and Sharples marked his first Twickenham start with his first Test try.
The Gloucester wing collected Goode's offload and cut in-field, wriggling and driving his way through three Fijian defenders before stretching for the line.
Johnson, debutant Tom Youngs and captain Chris Robshaw all carried powerfully to keep England on the front foot and Fiji's only answer to the pressure was to spoil.
Flood added a second penalty, taking his Test points tally past the 250 mark, before Fiji captain Manu was sin-binned but England were guilty of butchering chances.
England failed to control their own five-metre scrum and when they spread the ball wide, the final pass from Joe Marler to Brad Barritt went forward and straight into touch.
This was not the clinical execution coach Andy Farrell had demanded but England's pressure was too much for Fiji to bear.
When Robshaw was held up over the line, the pack England remained disciplined and twice shoved Fiji backwards to earn the penalty try.
Fiji received a let-off when Sharples' chip ahead just brushed the in-goal whitewash before he could touch it down but England kept coming.
Care was scragged just short of the line but Fiji conceded yet another penalty and Monye benefited from the quick tap to score on his first England appearance in over two years.
Flood extended England's lead with a penalty soon after the restart and ran at Fiji again, with Tuilagi and then Care making a dart for the line.
England spread the ball wide and Dan Cole crashed over the line in search of his second international try but the television official ruled he had been held up.
Saracens prop Mako Vunipola was sent on for his debut and England built from the attacking platform, working an overlap down the left and Robshaw sent Johnson over for his first Test try.
England switched off and allowed Fiji to score an eye-catching consolation, with Malaki Ravulo streaking away from Tuilagi before Talebula kicked ahead to score.
Flood then scuffed the kick-off, to cap an unceremonious couple of minutes but they were soon back in the groove with Monye benefiting from Barritt's decoy run to cut an excellent line.
Flood then exploited the space out left, launching a long pass for Sharples, who stepped inside his men and scored his second try of the match.
England began to ring the changes and Ben Youngs came on to join his elder brother Tom, who produced an impressive Test debut before making way for David Paice.
Ben Youngs and Mike Brown both dropped the ball over the line as England looked to turn the screw against a tiring Fiji team.
Qera somehow managed to haul down a barnstorming run from Waldrom but Fiji were stretched again as quick hands from Barritt allowed Tuilagi to dive over in the corner.
The Leicester centre then brushed aside a weak tackle to touch down again but Fiji had the final word, with Seko Kalou crashing over for their second try.
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