Maharaj last played an ODI back in 2018 but has been rewarded for his stellar displays in the Momentum One Day Cup, where he is the joint-highest wicket-taker with 13 wickets.
Former skipper Faf du Plessis has been rested once again along with Rassie van der Dussen and Dwaine Pretorius.
Du Plessis also missed the ODI series against England, which ended 1-1.
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Head coach Mark Boucher explained that Du Plessis remains an integral part of South Africa's ODI plans going forward, but he is also keen on providing promising youngsters an opportunity to shine.
"Faf (du Plessis) has been fantastic for us in white-ball cricket and remains very much in our ODI plans and we will manage his workload for the near future diligently. I would like to strengthen our depth pool right now and see what players we have out there. I feel that this is the time and opportunity to do so."
While the likes of Kyle Verreynne and Janneman Malan have been included in the side, 19-year-old speedster Thando Ntini was surprisingly overlooked despite his impressive performances for the Cobras in the One Day Cup.
The first game of the series will be played at Paarl on February 29 following which the action will shift to Bloemfontein for the second ODI on March 4.
South Africa's 15-man ODI squad: Quinton de Kock (c & wk), Temba Bavuma, David Miller, Kagiso Rabada, Andile Phehlukwayo, Tabraiz Shamsi, Lungi Ngidi, Beuran Hendricks, Heinrich Klaasen, Janneman Malan, Jon-Jon Smuts, Anrich Nortje, Lutho Sipamla, Keshav Maharaj, Kyle Verreynne.