Siakam was born in Douala, Cameroon, in 1994. He is the youngest of four brothers and was raised in a devoutly Catholic family. His father, Tchamo, worked for a local transit company and was also the mayor of Makénéné, a small town in Cameroon. According to a story by ESPN's Jackie MacMullan, Pascal was "hand-picked to embody his family's Catholicism," and his father enrolled him in St. Andrew's Seminary in Bafia at age eleven. However, by the time he was fifteen, he no longer wanted to become a Catholic priest.

Siakam initially had little interest in basketball, unlike his older brothers, who all earned scholarships with the sport to various NCAA Division I colleges. However, that changed when he was discovered at a local basketball camp by NBA player Luc Mbah a Moute, who was raised just a few miles from St. Andrew's. Siakam attended Mbah a Moute's camp for the first time in 2011, a year before graduating from St. Andrew's, and he returned the following year.

Siakam's apparent athleticism and high energy level at the Basketball Without Borders camp caught the attention of scouts, despite his lack of experience playing basketball at the time. With Mbah a Moute as a mentor, Siakam moved to the United States at the age of eighteen to pursue his dreams of playing basketball at a high level. He attended God's Academy in Lewisville, Texas, where he honed his skills and caught the attention of college recruiters.

Siakam eventually enrolled at New Mexico State University in 2013. After redshirting his freshman year due to injury, Siakam worked his way onto the Aggies' starting lineup and earned WAC Freshman of the Year honors by the 2014-15 campaign. He continued to improve, averaging 20.2 points, 11.6 rebounds, and 2.2 blocks per game in his sophomore year and earning unanimous WAC Player of the Year honors.

On April 19, 2016, Siakam declared for the NBA draft, forgoing his final two years of college eligibility. The Toronto Raptors selected him with the 27th overall pick in the first round of the draft, and he quickly became a fan favorite due to his impressive performances on the court. Today, he is one of the best players in the NBA and a key contributor to the Raptors' success.