Henson has been given the chance by Warren Gatland to press his claims for World Cup selection, having missed out on the tournaments in both 2003 and 2007.
The 29-year-old - who currently does not have a club for next season - starts in midfield alongside Cardiff's Jamie Roberts, who shifts to outside centre.
There are three other changes made by Gatland from the side that lost the reverse fixture 23-19 at Twickenham last weekend.
James Hook is drafted in at full-back to replace the desperately unlucky Morgan Stoddart, who suffered a broken leg during the defeat to England and will now miss the World Cup.
The other alterations are up front, where Newport Gwent Dragons hooker Lloyd Burns is handed a first Test start, and his club-mate, lock Luke Charteris, takes over from Bradley Davies in the second row.
"We need the win this weekend - it's as simple as that," said Gatland.
"We've told the players that, for us to be regarded as contenders at the Rugby World Cup, we need to beat England at home this weekend, to send out that message to everyone that we are contenders.
"We have the toughest pool at the tournament and in less than a month's time we will be facing South Africa in our opening match.
"It is vitally important that we go into that match with the sound of Welsh fans ringing in our ears, fans who have cheered us on to victories in the final two matches of our warm-up campaign against England and against Argentina next week.
"We have retained the majority of the side who travelled to London last week and told them that we want more of the same.
"There are one or two players we have brought in to have a look at but the reason we have deliberately not made wholesale changes is that we need to win this game and we believe these are the players who can do that."
Scarlets' Rhys Priestland continues at fly-half and flanker Sam Warburton will again skipper the side from the back row.
Gatland has also named young forwards Josh Turnbull and Justin Tipuric on the bench, but ex-captain Ryan Jones is ruled out because of a calf problem.
Wales team:
J Hook (Perpignan); G North (Scarlets), J Roberts (Cardiff Blues), G Henson (unattached), Shane Williams (Ospreys); R Priestland (Scarlets), M Phillips (Bayonne); P James (Ospreys), L Burns (Newport Gwent Dragons), C Mitchell (Exeter), L Charteris (Newport Gwent Dragons), AW Jones (Ospreys), D Lydiate (Newport Gwent Dragons), S Warburton (Cardiff Blues, captain), T Faletau (Newport Gwent Dragons).
Replacements: H Bennett (Ospreys), R Bevington (Ospreys), J Turnbull (Scarlets), J Tipuric (Ospreys), T Knoyle (Scarlets), Scott Williams (Scarlets), A Brew (Newport Gwent Dragons).
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