The four-time champion crossed the line in the 46 kilometre stage in a time of two hours, 59 minutes and 33 seconds (2:59.33), well ahead of the defending K1 winner Kime (3:04.37).
That put Birkett well ahead with an overall time of 5:35.59, with the final stage from Inanda Dam to Blue Lagoon on Saturday.
Sbonele Khwela maintained his third position, although he had fallen even further back following a time of 3:07.24 – his overall time being 5:45.45.
Yet the stage, which is the longest in the three-day race covering 46 kilometres from the start at Dusi Bridge, appeared to be much tighter after Kime and Khwela held their own for most of the way.
Birkett was slowly drifting away by the time they got to Nqumeni Hill Portage – the lead before he left the water was over three minutes between first and third.
But by the time they returned to the water, Khwela. Whose strong point is running with the boat, closed to just over two minutes behind.
That, though, was as close as it got as Birkett began to pull away again.
He entered the final 11 kilometre stretch of flat water at the dam around two and a half minutes ahead of Kime and four ahead of Khwela.
By the finish, he was well on his way towards securing a fifth Dusi crown and second individual title.
Three-time runner-up Laura O’Donoghue maintained her dominance of the women’s race as she swept aside the field to win stage two in a time of 3:35.31, over 20 minutes ahead of Cana Peek.