In the absence of Rob Kearney, Zebo again starts at 15 having produced a man of the match performance in the position in last month's victory over Scotland.
With Kearney likely to be Ireland's first-choice fullback in the World Cup, Zebo will hope a good showing on Saturday will boost his chances of matchday inclusion in the tournament. As he is also in with a shot on the wing and his versatility could work in his favour.
Prop Cian Healy has not been risked as he recovers from injury, meaning he will go into the World Cup without playing in any of the warm-up games.
Rory Best returns at hooker for his first start of the campaign while Jared Payne comes back into the side to renew his centre partnership with Robbie Henshaw, with Conor Murray and Jonathan Sexton the halfbacks.
Paul O'Connell captains the team and is partnered in the second row by Devin Toner.
After losing at home to Wales last week Ireland will be desperate to get back on track ahead of their World Cup opener against Canada on September 19.
Ireland beat England in the Six Nations in Dublin in March but have lost on their last two visits to Twickenham.
Ireland team:
15-Simon Zebo, 14-Tommy Bowe, 13-Jared Payne, 12-Robbie Henshaw, 11-Dave Kearney, 10-Jonathan Sexton, 9-Conor Murray; 8-Jamie Heaslip, 7-Sean O'Brien, 6-Peter O'Mahony, 5-Paul O'Connell (captain), 4-Devin Toner, 3-Mike Ross, 2-Rory Best, 1-Jack McGrath.
Reserves:
16-Richardt Strauss, 17-Tadhg Furlong, 18-Nathan White, 19-Donnacha Ryan, 20-Chris Henry, 21-Eoin Reddan, 22-Ian Madigan, 23-Darren Cave.
