Objective: The purpose of this study was to compare the marginal gap of E-max press, and E.max computer-aided design and computer-assisted manufacturing (CAD-CAM) lithium disilicate (LD) ceramic crowns fabricated by using conventional technique and CAD-CAM technique. Materials and Methods: This was an in vitro experimental study carried out in Riyadh Elm University and King Saud University. A marginal gap of 30 LD crowns was evaluated by Stereomicroscopy. A total of 15 pressable LD (IPS E.max Press [Ivoclar Vivadent]) ceramic crowns were fabricated by using conventional lost wax pattern method (Group A). Digital impressions of the prepared dies were scanned and transferred to the milling machine. IPS E.max CAD (IPS E-max, Ivoclar, Amherst, NY, USA) LD blocks in shade Vita A2 were then milled by using DWX-50 machine for CAD-CAM crowns (Group B). Descriptive statistics of mean and standard error of marginal gaps for both groups were recorded and compared by applying Mann–Whitney U-test. All the data were analyzed by using statistical analysis software SPSS version 21.0 (Armonk, NY, USA: IBM Corp). Results: The LD crowns prepared by CAD-CAM technology (26.80 ± 3.4 μm) had significantly lower ( P < 0.001) marginal gap than the LD pressed crowns (38.8 ± 2.3 μm) fabricated by conventional technique. The marginal gaps between CAD-CAM versus conventional groups exhibited significant differences at (42.68 μm vs. 52.46 μm, U = 51.500, P = 0.011), Mesiobuccal (15.94 μm vs. 30.13 μm, U = 45.500, P = 0.005), distolingual (26.70 μm vs. 43.86 μm, U = 63.500, P = 0.042), and distal (12.38 μm vs 31.45 μm, U = 47.500, P = 0.006). Conclusions: Within the limitations of the study, it can be concluded that LD all ceramic crowns fabricated by using CAD-CAM techniques showed lesser marginal gap and better marginal fit compared to the conventional technique.