To evaluate the fatigue failure load (FFL), number of cycles for failure (CFF) and survival probabilities of lithium-disilicate (LD) monolithic crowns manufactured by two processing techniques (pressing vs. CAD/CAM) adhesively cemented to a dentin-analogue material, considering two surface treatments (conventional vs. simplified). Surface characteristics (topography, roughness and fractal dimensions) were also assessed. Forty (40) monolithic crowns were manufactured considering two specific processing techniques for each ceramic system: LD - CAD/CAM lithium-disilicate (IPS e.max CAD, Ivoclar Vivadent); LD - pressed lithium-disilicate (IPS e.max Press, Ivoclar Vivadent). The crowns were adhesively cemented (Multilink Automix System, Ivoclar Vivadent) onto dentin analogue preparations considering two distinct protocols of surface treatments (conventional - hydrofluoric acid etching + silane application [HF+Sil] or simplified - etching with one-step primer (Monobond Etch&Prime, Ivoclar Vivadent) [EP]). The cemented assembly was stored in distilled water at 37 °C for 3 days and fatigue tests were run (step-stress approach: load ranging from 400 to 2000 N, step-size of 100 N, 15,000 cycles/step, 20 Hz). Fractography, surface topography, roughness, and fractal dimension analyses were performed. LD[EP] group depicted higher FFL, CFF and survival probabilities in comparison to LD groups, regardless of the conditioning method. A tendency of higher Weibull modulus (mechanical reliability) was observed when using [EP] for both LD and LD. SEM and AFM analysis showed very distinct initial surface patterns for the distinct processing techniques considered (LD with higher fractal dimension and lower roughness than LD), and both surface treatments distinctly affected these surface characteristics. All failures were radial cracks originating at the ceramic-cement interface. Pressed lithium-disilicate monolithic crowns showed better fatigue performance in comparison to CAD/CAM milled crowns, especially when they were treated with self-etching ceramic primer. The surface treatment with self-etching primer led to similar fatigue performance when compared to hydrofluoric acid plus silane application for the same processing technique, but it tended to provide higher mechanical reliability.