The club was originally founded in 1945. Lokomotiv saw little success for the majority of its history, usually competing in the second or third tiers of Bulgarian football. In 2008, the team achieved a historic first promotion to the A Group, (now known as First League). Lokomotiv Mezdra managed to survive two seasons in the elite, before suffering relegation after the 2009-10 season. In the following years, financial problems overwhelmed the club, forcing its folding in 2012. The team was re-founded in 2016, starting from the regional amateur fourth tier.