The Leicester Tigers fly-half converted two tries from Northampton Saints wing Chris Ashton and added three penalties from three attempts as England got off to a winning start at the Millennium Stadium.
Flood, who started the game alongside Tigers clubmates Ben Youngs, Dan Cole and Louis Deacon, was replaced by Jonny Wilkinson in the last quarter of an hour.
Martin Castrogiovanni was within three minutes of maintaining an unbeaten start to the Six Nations for Tigers players on Saturday afternoon as Italy led Ireland in Rome. But then a drop goal from replacement Ronan O'Gara tipped the game Ireland's way, 13-11.
Tigers duo Billy Twelvetrees and Manu Tuilagi started a second successive game as centre partners for England Saxons but could not build on last week’s win over Italy A as they were beaten 20-11 by Irish Wolfhounds at Ravenhill in Belfast.
Ugo Monye scored the Saxons try with the rest of the points coming from the boot of Stephen Myler.
The Wolfhounds, who included former Tigers favourites Ian Humphreys and Johne Murphy, scored tries through Denis Hurley and captain Chris Henry. Humphreys finished with a 10-point haul, including a second-half drop goal.