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Background We evaluated the efficacy of a new anesthetic technique termed ultrasound-guided capsule-sheath space block (CSSB) combined with anterior cervical cutaneous nerve block (CCNB) for thyroidectomy. Methods The study included two parts: Part one was an imaging study to determine technique feasibility. The CSSB was performed on five healthy volunteers by introducing the needle 0.5 cm lateral to the probe under in-plane needle ultrasound guidance. After puncture of the false capsule and its subsequent contraction with the true capsule of thyroid, 10 mL of contrast medium was deposited slowly in the capsule-sheath space. The CCNB was performed bilaterally as follows: Under ultrasound guidance, a subcutaneous injection was made along the sternocleidomastoid using 10 mL of contrast medium which was followed by a girdle-shaped picchu raised from the cricoid cartilage to supraclavicular region. The spreading pattern of contrast medium was imaged using computed tomographic scanning. In part two (a clinical case series) the technique efficacy was evaluated. Seventy-eight patients undergoing thyroidectomy had ultrasound-guided CSSB and CCNB with local anesthetics. The sensory onset of CCNB, intraoperative hemodynamic parameters, and analgesic effect were assessed and complications were noted. Results The distribution of contrast medium was well defined. In part two the onset time of CCNB was 2.2 ± 0.7 min, and the hemodynamic parameters remained stable intraoperatively. The recall of visual analogue scale scores during surgery was 2 [1–4] for median (range). The patients’ and surgeons’ satisfaction scores were 2 [1–4] and 1 [1–3] for median (range). No serious complications occurred. Conclusions Combining ultrasound-guided CSSB and CCNB is a feasible, effective and safe technique for thyroidectomy. Trial registration Current Controlled Trials ChiCTR-ONC-12002025. Registered 19 March 2012.