Background Post-thoracotomy pain can be severe and difficult to control. Paravertebral block (PVB) has been proven to be effective in controlling post-thoracotomy pain; however, it has its own set of complications. Ultrasound-guided serratus plane block (SPB) is a newly described field block that may provide thoracic wall analgesia. Objective This prospective randomized controlled study was carried out to compare the analgesic effects of PVB and SPB on post-thoracotomy pain. Patients and methods The study was done on 60 adult patients aged 18–65 years undergoing thoracotomy for pulmonary resection. The patients were randomly allocated to receive either thoracic PVB or SPB guided by ultrasound before induction of general anesthesia. The primary outcome was the visual analogue scale, which was recorded on arrival to the ICU and then at 1, 2, 4, 8, 12, 18, and 24 h postoperatively both at rest and during coughing. The secondary outcomes were time to perform the block, onset of sensory block, number of blocked dermatomes, block success rate, total postoperative morphine consumption, and any complications related to the regional block. Results The time to perform the block was significantly shorter in SPB than in PVB (3.76±1.1 vs. 6.14±1.6 min, P<0.05). The onset of complete sensory block was significantly faster with SPB than with PVB (14.3±2.8 vs. 17.6±3.5 min, P<0.05). The visual analogue scale was also comparable between the two blocks at all measuring times except at 12 and 18 h postoperatively, where it was significantly higher with SPB than with PVB during coughing (P<0.05). The total postoperative morphine consumption was significantly lower in the PVB group than in the SPB group (13.2±2.6 vs. 18.4±1.8 mg, P<0.05). There was no significant difference between the two blocks regarding complications. Conclusion SPB had a shorter time to perform and a faster onset of action than thoracic PVB and provided adequate analgesia in the early postoperative period; however, postoperative morphine consumption was higher in patients who received SPB.