Liam Dawson will make only his second England Test appearance and Gary Ballance will bat at number three in the first game of the four-match series against South Africa.
Dawson was handed a Test debut in India last December and will make his first appearance on home soil in the longest format at Lord's after being named in the side for the series-opener, which starts on Thursday.
The inclusion of both Dawson and Moeen Ali marks the first time in 24 years that England have named two spinners for a Test at Lord's.
Ballance returns to the international stage after being absent since last October and will come in at the fall of the first wicket, with Joe Root dropping down a place to number four in his first Test as captain and Jonny Bairstow at five.
Seamer Toby Roland-Jones misses out on a Test debut on his home ground as Mark Wood returns to an attack which includes Stuart Broad, who has recovered from a heel injury, and James Anderson.
England team: Joe Root (captain), Moeen Ali, James Anderson, Jonny Bairstow, Gary Ballance, Stuart Broad, Alastair Cook, Liam Dawson, Keaton Jennings, Ben Stokes, Mark Wood.