Coffea canephora is responsible for over 40% of global production and holds industrial relevance, especially in the production of soluble coffee. However, issues related to beverage quality still need improvement to meet the demand for high-quality coffees. This study investigated chemical and sensory changes in Coffea canephora var. conilon during Self-induced Anaerobiosis Fermentation (SIAF) versus Conventional processing, with or without starter yeasts. Hanseniaspora opuntiae and Meyerozyma caribbica populations were monitored using qPCR, while sugar and acid concentrations were measured by HPLC. Pulped coffees showed higher sugar consumption (71%–79%) than natural ones (12%–24%) during 72 h of SIAF, with lactic acid uniquely present in SIAF treatments. GC-MS identified 35 volatile compounds in roasted coffees, with esters and ketones differing between SIAF and Conventional treatments. Ethyl isovalerate and ethyl palmitate were found only in Natural SIAF inoculated with H. opuntiae, which received the highest cupping score (82 points). Consumers perceived all Natural SIAF coffees as distinct from Natural Conventional. In Natural SIAF coffee, H. opuntiae contributed to an exotic and fruity profile, while in Pulped SIAF, M. caribbica yielded a balanced and mild coffee. The SIAF method, with or without yeast addition, holds the potential for producing specialty Canephora coffee.