Background Greater occipital nerve (GON) blocks are widely used for the treatment of headaches, but quality evidence regarding their efficacy is scarce. Objective The objective of this article is to assess the short-term clinical efficacy of GON anaesthetic blocks in chronic migraine (CM) and to analyse their effect on pressure pain thresholds (PPTs) in different territories. Participants and methods The study was designed as a double-blind, randomised, placebo-controlled clinical trial. Thirty-six women with CM were treated either with bilateral GON block with bupivacaine 0.5% ( n = 18) or a sham procedure with normal saline ( n = 18). Headache frequency was recorded a week after and before the procedure. PPT was measured in cephalic points (supraorbital, infraorbital and mental nerves) and extracephalic points (hand, leg) just before the injection (T0), one hour later (T1) and one week later (T2). Results Anaesthetic block was superior to placebo in reducing the number of days per week with moderate-or-severe headache (MANOVA; p = 0.027), or any headache ( p = 0.04). Overall, PPTs increased after anaesthetic block and decreased after placebo; after the intervention, PPT differences between baseline and T1/T2 among groups were statistically significant for the supraorbital (T0-T1, p = 0.022; T0-T2, p = 0.031) and infraorbital sites (T0-T1, p = 0.013; T0-T2, p = 0.005). Conclusions GON anaesthetic blocks appear to be effective in the short term in CM, as measured by a reduction in the number of days with moderate-to-severe headache or any headache during the week following injection. GON block is followed by an increase in PPTs in the trigeminal area, suggesting an effect on central sensitisation at the trigeminal nucleus caudalis. This trial is registered at ClinicalTrials.gov (NCT02188394).