Setsile was born in 1978 in the village of Parakarungu, Chobe, Botswana. Growing up in an area rich with wildlife, he developed a deep passion for animals from a young age. Setsile began his primary education in Parakarungu and continued as a boarding student at Chobe Secondary School in Kasane, a town close to Africa's 'Four Corners' where the borders of Botswana, Namibia, Zambia and Zimbabwe almost meet. The school’s proximity to a hotel travelers frequented allowed him to observe guides with their guests, inspiring him to pursue a career in guiding.

After completing his education, Setsile trained as a guide at Chobe Game Lodge. He joined Wilderness Safaris in 2004 as a junior guide at Baobab Safari Lodge, where he worked until 2006. He then moved to Duba Plains Camp, guiding there from 2006 to 2008. From 2008, he served as a senior guide at Vumbura Plains until 2021. In 2021, Setsile transferred to Mombo Camp, Wilderness Safaris' flagship camp in the Okavango Delta, where he continues to work to date. In 2024, Setsile was delighted to become a Nat Hab Expedition Leader in Southern Africa. In his leisure time, he loves watching football.