The isolated second metacarpal base fracture-dislocations in adults are rare, and the traditional main treatments include closed reduction with the plaster or splint and open reduction with internal fixation (ORIF). However, closed reduction with the plaster or splint is not solid enough and ORIF can damage the surrounding important tissues. The purpose of this study was to explore the clinical outcomes of closed reduction and external fixation (CREF) for the treatment of isolated second metacarpal base fracture-dislocations. Ten patients who suffered isolated second metacarpal base fracture-dislocations between January 1, 2010, and February 1, 2020, were reviewed. All of the patients were treated by CREF. Radiographs and computed tomography scans were performed regularly after the operation. The grip and pinch strength, visual analog scale (VAS) pain score, American Society for Surgery of the Hand total active movement (TAM) and total active flexion (TAF) scores, Cooney score, Sollerman hand function test (SHFT) score, QuickDASH score, and range of motion of the index finger were recorded at the last follow-up visit to evaluate functional recovery; the injured and healthy hands were compared and we also recorded postoperative complications. The paired samples t-test was used to compare the healthy and injured sides. The patients were followed up for a median of 29.50 ± 4.2 months. There were no significant differences in the grip strength, pinch strength, angle of proximal interphalangeal joint (PIPJ) flexion, or angle of distal interphalangeal joint (DIPJ) flexion between the injured and healthy sides at the final follow-up visit (all p > 0.05). The mean TAM (268.20 ± 4.21) and TAF scores (270.60 ± 4.17) on injured side were significantly lower than those on healthy side (all p < 0.05). The mean Cooney score (93.50 ± 7.47) and SHFT score (78.50 ± 1.08) on injured side were lower, while the mean QuickDASH score (7.05 ± 3.11) on injured side was higher than those on healthy side (all p < 0.05). The mean VAS pain score was 0.50 ± 0.53 on injured side. There were no significant postoperative complications except for traumatic arthritis in one patient without obvious clinical symptoms. CREF achieves the satisfactory curative effect, and the patients obtain the good functional recovery without significant postoperative complications. CREF is a safe and effective treatment for isolated second metacarpal base fracture-dislocations with satisfactory clinical outcomes.