The 21-year-old athlete confirmed her prowess in the fast lane by claiming the title for the second straight year, scorching through the tape in what was a meeting record of 16.96 seconds.
She was followed home by Banele Shabangu (Tshwane University of Technology) in 17.34 and Boipelo Tshemese (Tuks) in 17.43.
The Newton Classic Shootout takes place each year at the beginning of the season and presents unfamiliar distances for the athletes, such as 60m, 150m and 300m. It was held at the University of Johannesburg Stadium.
Nekhubui was overjoyed with her performance.
"Defending my title from 2021 and improving my personal best time was a great feeling, but also very humbling as there is a phenomenal team behind me who have helped me reach this achievement."
She added that her strategy was simple – just run as fast as you can.
"I don't have any real tactics for the 150m. I think it's all about running flat out and to keep your shape until the finishing line.
"I don't feel that I have any challenges in running this race as all I try to do is to focus on my own performance and not to panic as I am not a particularly fast starter."
Nekhubui was born in Tswera Mashishi, a small town in Limpopo, and was spotted by Nkwalu Sports Management when she participated in school competitions in 2015.
After being based in Johannesburg – she won the 150m Newton Classic race under the Tuks banner last year – she has since moved to Gqeberha.
"I am being coached by Gerrie Posthumus, who has polished my skills and made the journey enjoyable," she said.
"I have a training partner in (Madibaz sprinter) Luxolo Adams, who has contributed to my motivation. This is how I have come to represent Madibaz."
Nekhubui, whose favourite sprinting distance is the 200m, said her interest in running was ignited by seeing South African athletes in newspapers and on television winning international titles.
"I was especially enthralled when the athletes came from the same background as me," she added.
"This sparked my passion and drive, which is to inspire young athletes, especially athletes from my hometown and those who are resource-challenged. I hope to change the world of sports for them."
She competed in Europe last year, which she said saw her career developing in the right direction.
"My goal now is to stay injury-free because that allows you to do anything, and I can achieve more than I anticipate.
"I am also working towards participating in major competitions, such as the World Champs, African Champs and the Diamond League."