They finished at 119 for one with former captain Alastair Cook unbeaten on 59.
The tourists had been dismissed for 361 with spinners taking six of the wickets, four of them to Moeen Ali for 59.
Resuming at 214 for five, South Africa fought hard to stay in contention, especially through Quinton de Kock and Vernon Philander, who made half-centuries and added 66 for the eighth wicket.
De Kock ended Stuart Broad's involvement in England's bowling attack, striking 10 fours in his 51, which at 36 balls was the second fastest half-century in a Lord's test.
A fine low catch by Ben Stokes ended his innings but Philander stuck around long enough to make 52 despite having been hit on the hand by Jimmy Anderson.
He went to hospital for an x-ray which showed no break. It was though a further blow to South Africa, who will have fellow paceman Kagiso Rabada suspended for the second test next week for using "inappropriate language" on the opening day.
Nightwatchman Rabada and fellow overnight batsman Temba Bavuma went in successive overs to spinners Liam Dawson and Moeen after playing out the first 10 overs of the day.
Rabada edged the ball to wicket-keeper Jonny Bairstow to give Dawson his first test wicket in England.
Bavuma, having made 59 off 130 balls, was taken at slip by Stokes and in his disappointment headed off in the wrong direction for the pavilion before realising his error.
Broad wasted the new ball and lasted only four overs, which cost 35 runs, most of them in boundaries by De Kock.
Philander was last out after reducing the lead to under 100 but was unable to bowl when England batted again.
Morne Morkel and Rabada kept the openers quiet early on and Cook twice survived a review for leg before.
Either side of tea, however, South Africa's depleted attack found the going tougher and it took them until the 35th over of the innings to break England's opening stand of 80.
Keaton Jennings edged Morkel to wicketkeeper De Kock, having made 33 but Garry Balance, 22 not out at the close, helped Cook push the lead beyond 200.
(Reporting by Steve Tongue; Editing by Ken Ferris)
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