This paper presents a self-adaptive neuro-fuzzy inference system (SANFIS) that is capable of self-adapting and self-organizing its internal structure to acquire a parsimonious rule-base for interpreting the embedded knowledge of a system from the given training data set. A connectionist topology of fuzzy basis functions with their universal approximation capability is served as a fundamental SANFIS architecture that provides an elasticity to be extended to all existing fuzzy models whose consequent could be fuzzy term sets, fuzzy singletons, or functions of linear combination of input variables. Without a priori knowledge of the distribution of the training data set, a novel mapping-constrained agglomerative clustering algorithm is devised to reveal the true cluster configuration in a single pass for an initial SANFIS construction, estimating the location and variance of each cluster. Subsequently, a fast recursive linear/nonlinear least-squares algorithm is performed to further accelerate the learning convergence and improve the system performance. Good generalization capability, fast learning convergence and compact comprehensible knowledge representation summarize the strength of SANFIS. Computer simulations for the Iris, Wisconsin breast cancer, and wine classifications show that SANFIS achieves significant improvements in terms of learning convergence, higher accuracy in recognition, and a parsimonious architecture.