Simon Brazier will leave the firm at the end of May after eight years.
The company said he has made a significant contribution to the growth of its quality team, and he will take some time to consider the next step in his career.
Brazier (pictured) co-manages the Ninety One UK Alpha fund alongside Anna Farmbrough, who will replace Brazier alongside Ben Needham.
The pair will also co-manage Ninety One’s UK equity income strategies.
A spokesperson for Ninety One said: "We are very grateful to Simon and wish him all the best.
"There will be no impact to the quality team’s global strategies...Ben and Anna have significant experience in UK equities, and we are excited about the opportunity for the UK Alpha and UK Equity Income funds under their joint leadership."
The alpha fund lost 6.8 per cent in 2022, beating its benchmark by 0.4 percentage points but underperforming the wider UK large cap equity fund sector by 2 percentage points.
Over the past five years it has beaten its benchmark and the wider sector, returning 2.89 per cent compared to the index’s loss of 2.7 per cent.
Brazier previously worked for Threadneedle as head of UK equities alongside managing the Threadneedle UK fund, and spent time at Schroders.