Despite a run rate that remained stubbornly below three an over, the day offered an intriguing balance between bat and ball, with South Africa's bowlers holding England's batsmen in check for the most part, half-centuries from Joe Root and Ben Stokes notwithstanding.
England won the first and third Tests by big margins of 211 runs and 239 runs respectively.
Temba Bavuma was 30 not out and Faf du Plessis, the South Africa captain, six not out, with the Proteas needing a win in Manchester if they were to end this four-match series all square at 2-2.
After Root's departure, Stokes found an able partner in Bairstow and the duo took England past 250-run mark thanks to the 65-run partnership between them.
However, Morne Morkel and Rabada set South Africa's example with the new ball, hammering out an edge-threatening line and length to England's brace of left-handed openers, before Duanne Olivier provided pace, enthusiasm and the odd unplayable delivery in a lively return to the ranks. We let ourselves down with the bat in the first innings, and we have been brutally honest about it.
After several overs of determined defence, a mix-up almost saw Bavuma run out only for bowler Moeen Ali to miss the stumps as he gathered a throw from mid-off.
In the next over from Moeen, England would have got De Kock for just a single if Ben Stokes had clung on to another sharp one from an edged cut to slip.
Earlier, Bairstow, resuming on 33 and with England looking to build on an overnight score of 260-6, thrilled the crowd and tormented South Africa with an irresistible combination of judgement, shot selection and execution.
Jennings exited for 17, the only wicket to fall in a session that saw England reach lunch on 67 for one against a Proteas attack missing Vernon Philander and Chris Morris after both pacemen were ruled out with lower back strains.
South Africa enjoyed a more productive time in the afternoon session, driven forward by Rabada's infectious energy and Maharaj's craft.
Anderson may have turned 35 last Sunday and the re-naming of Old Trafford's Pavilion End in his honour may have felt like a gesture towards a man who is nearing the end of his career.
This was an exemplary Test innings - executed to perfection from first ball to last - and it showed just how mature a player Stokes has become.
England off-spinner Moeen Khan also made some history of his own by taking a hat trick - the first at the hallowed London venue and the South Africans also made some unwanted history. In the end, he fell one run short, becoming the 13th England Test batsman to be dismissed for 99.
Anderson's quartet of scalps came after he helped Jonny Bairstow put on 50 for the tenth wicket in England's first innings - although it should be noted that his contribution was just four not out!