Moeen Ali, dropped on 15 — arguably the easiest of five catches the Proteas put down on Sunday — top-scored with 75 not out.
Ali faced 66 balls including nine fours and three sixes.
Morne Morkel took two wickets for one run in four balls on Monday as he dismissed Stuart Broad and James Anderson to end the innings after England resumed on their overnight 224 for eight.
The tall fast bowler led South Africa’s attack with four for 41 in 13.1 overs.
South Africa need to set a new ground record if they are to end this four-match series all square at 2-2, with England’s 294 for four against New Zealand in 2008 the most any side have yet made to win in the fourth innings of a Test at Old Trafford.
The corresponding South Africa record is 414 for four — the second-highest fourth-innings total to win a Test of all-time — against Australia at Perth in 2008.
Hashim Amla, playing at Old Trafford, made 53 in that innings.
But just as the players were walking back on for the start of South Africa’s second innings, rain lashed down on Old Trafford and stopped play before a ball had been bowled in the Proteas’ chase.
Conditions improved, however, and play resumed at 12:10pm local time (1110 GMT).
Lunch will now be taken at 1230 GMT and tea at 1540 GMT.
There are a minimum of 89 overs left in the day’s play, with the scheduled close now put back to 1800 GMT.
South Africa have not lost a Test series in England since 1998 and in their past 19 away Test series they have suffered just one campaign reverse — against India in 2015/16.
If England avoid defeat in this match, they will give Joe Root victory in his first Test series as England captain.
The England team wore black armbands on Monday in memory of Doug Insole, whose death at the age of 91 was announced on Sunday.
A former Essex and England batsman, Insole was a Test selector for nearly 20 years and an influential administrator.