Background Tranexamic acid (TXA) in oral, topical, and intra‐dermal injection routes showed efficacy in melasma treatment. Micro‐needling and fractional carbon dioxide (CO2) laser were reported to enhance the drug delivery of TXA. Aims This study aimed at comparing the use of micro‐needling and fractional CO2 laser for drug delivery of TXA in the treatment of facial melasma. Patients/Methods Thirty female patients with bilateral symmetrical facial melasma were subjected to micro‐needling, for one side of the face, and fractional CO2 laser, for the other, followed by an immediate topical application of TXA solution 4 mg/mL. Patients received six biweekly sessions. Results Two weeks after the last session, a significant reduction in baseline modified melasma area and severity index (mMASI) score was observed on both sides. The mean ± SD baseline mMASI dropped from 3.43 ± 1.84 to 1.59 ± 1.51 (mean reduction 57.73%, P < .001) and from 3.51 ± 1.84 to 1.78 ± 1.51 (mean reduction 55.82%, P < .001) in the micro‐needling–treated side and in the fractional CO2 laser–treated side, respectively. However, no statistically significant differences were found between the two sides (P = .81). Conclusions Micro‐needling and fractional CO2 laser are equally safe and effective for the delivery of TXA in the treatment of facial melasma.