Pieter Malan hit an unbeaten 195 on Wednesday as the Cobras opened up a 201-run lead over the Knights in Cape Town.
After dismissing the Bloemfontein outfit for only 181 on day one, Malan took control of the innings, helping the Cobras pile on the runs.
The home side reached stumps on 382-3 with Kyle Verreynne unbeaten at the other end on 74.
The Dolphins resumed day two on 67-2 after cleaning up the Warriors for only 124 on Tuesday, eager to build towards a big lead.
Khaya Zondo struck a superb 111, while Senuran Muthusamy made 52 and Keshav Maharaj added 66 before the Dolphins were all out for 358.
The Warriors, however, made a much-better start to their second innings, Edward Moore (42) and Gihahn Cloete (39) guiding the men from Port Elizabeth to 88-0 at stumps.
In Johannesburg, rain had a profound impact on day two between the Lions and Titans. Start of play was delayed at the Wanderers but Aiden Markram’s rich form with the bat continued as he kicked on from his sound start.
The Proteas opener carried the Titans’ hopes of surpassing the Lions’ first-innings total of 206. Markram reached an unbeaten 85 with the Titans on 169-5, when bad light brought an early end to the day’s play.