Sanford chief executive Volker Kuntzsch will step down after seven years in the role, effective from next week.
The Sanford board said it would soon start an international search for a replacement.
In the interim, Sanford's Andre Gargiulo will be the acting chief executive.
Chairman Sir Rob McLeod said Kuntzsch had made a "transformational" impact on Sanford.
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"Volker has helped transform Sanford into a progressive, values-based company with an outstanding commitment to environmental sustainability and to Sanford's people," McLeod said in a statement.
"Over those last seven years we have made good progress on maximising the value of our fish products and diversifying our business, as well as turning our aquaculture business into a profitable and innovative unit," he said.
"As we now move towards a greater focus on consumer-driven innovation and marketing, Volker and the Sanford board have agreed that now would be a sensible time for a new leader to drive the next phase of the strategy," McLeod said.
Sanford's shares last traded at $5.78, down 17c or 2.8 per cent, in a rising market.
Early this month, Sanford said Covid-19 dragged its third-quarter sales down by 15 per cent.
Volatility in global markets as a result of the pandemic was an ongoing challenge for the significant food service component of Sanford's business, but the company said it was making progress on the strategic changes needed to meet the new market conditions.
Kuntzsch said at the time the lockdowns around the world have had an "inevitable" effect.