Acute low back pain (LBP) imposes a significant socioeconomical burden as it is the condition that, worldwide, cause the most disability. Nonetheless, the literature regarding the best pharmacological management of acute LBP is limited, and the indications available in the literature are conflicting. This work investigates whether the pharmacological management of acute LBP can effectively reduce pain and disability, and aims to identify which drugs show the highest efficacy. This systematic review was conducted according to the 2020 PRISMA statement. In September 2022, PubMed, Scopus, and Web of Science were accessed. All the randomized controlled trials investigating the efficacy of myorelaxants, nonsteroidal anti-inflammatory drugs (NSAIDs), and paracetamol for acute LPB were accessed. Only studies that investigated the lumbar spine were included. Only studies reporting on patients with acute LBP with symptom duration of less than 12 weeks were included. Only patients older than 18 years and with nonspecific low back pain were included. Studies that investigated the use of opioids in acute LBP were not considered. Data from 18 studies and 3478 patients were available. Myorelaxants and NSAIDs were effective in reducing pain and disability in acute LBP at approximately one week. The combination of NSAIDs and paracetamol was associated with a greater improvement than the use of NSAIDs alone, but paracetamol alone did not induce any significant improvement. Placebo was not effective in reducing pain. Clinical Significance: Myorelaxants, NSAIDs, and NSAIDs with paracetamol could reduce pain and disability in patients with acute LBP.