The event traces its origins to a series of 300-kilometer races at the Shah Alam circuit organized by Malaysian automaker Proton, held to coincide with Malaysia's national Merdeka holiday. When the Sepang International Circuit opened, the race moved there. After a dispute between Proton and the circuit resulted in the manufacturer withdrawing its sponsorship following the 1999 edition, Sepang International Circuit chose to replace the event with the Merdeka Millennium 12 Hours Endurance Race from 2000, opening it to non-Proton entries for the first time.
The inaugural 2000 race was won by the Proton EON Racing Team with drivers Jimmy Low, Karamjit Singh, and Tommy Lee at the wheel.
In the early years the race was dominated by a mix of local and regional teams, with the Lotus Exige 300RR operated by Proton R3 Racing in cooperation with Amprex Motorsport winning in both 2005 and 2006. Amprex Motorsport, which also campaigned a GT1-specification Lamborghini Murcielago R-GT, provided the most technically ambitious entries of the mid-2000s though the car failed to finish in both its appearances.
The 2007 edition attracted the highest entry level in the race's history, with 103 cars registered and 77 reaching the starting grid — the limit set by the FIA circuit license granted to Sepang. That year also brought notable international names such as former Formula One and Le Mans driver Hans-Joachim Stuck to the grid.
In 2008, Porsche Club Singapore became the first foreign team to win the event outright when Darryl O'Young, Mok Wing Sun, and Alexander Davison took victory in a Porsche 997 RSR, completing 308 laps.
The race was renamed the Sepang 12 Hours in 2014. The following year, 2015, the Stephane Ratel Organisation — best known for setting global GT3 technical standards — assumed organisational control. The SRO positioned the race as the first of a sequence of major endurance events running through the Northern Hemisphere winter off-season, alongside the Dubai 24 Hour, the Rolex 24 at Daytona, and the Bathurst 12 Hour.
In 2016 the race served as the opening round of the newly created Intercontinental GT Challenge. The 2017 edition was cancelled due to insufficient entries, and the race has not been held in its original form since.
Tommy Lee is the only driver to have won the Open class three times, each time representing a different team: Proton EON Racing Team, TVR Racing, and Jaseri Racing.
The Honda Malaysia Racing Team won class A five consecutive times from 2003 to 2007 and also took the overall win in 2004, despite competing in class A rather than the outright-fastest class. Malaysian driver Jazeman Jaafar became the youngest participant in the event's history in 2007 at the age of 14. Porsche Club Singapore's 2008 victory was the first overall win by a foreign team.
After a five-year absence, it was announced in 2022 that the Sepang 12 Hours would return for 2023, organized through a partnership between Top Speed and Sepang International Circuit.