This study focuses on developing and evaluating efficient and effective parameter calibration and uncertainty methods for hydrologic modeling. Five single objective optimization algorithms and six multi-objective optimization algorithms were tested for automatic parameter calibration of the SWAT model. A new multi-objective optimization method (Multi-objective Particle Swarm and Optimization & Genetic Algorithms) that combines the strengths of different optimization algorithms was proposed. Based on the evaluation of the performances of different algorithms on three test cases, the new method consistently performed better than or close to the other algorithms. In order to save efforts of running the computationally intensive SWAT model, support vector machine (SVM) was used as a surrogate to approximate the behavior of SWAT. It was illustrated that combining SVM with Particle Swarm and Optimization can save efforts for parameter calibration of SWAT. Further, SVM was used as a surrogate to implement parameter uncertainty analysis fo SWAT. The results show that SVM helped save more than 50% of runs of the computationally intensive SWAT model The effect of model structure on the uncertainty estimation of streamflow simulation was examined through applying SWAT and Neural Network models. The 95% uncertainty intervals estimated by SWAT only include 20% of the observed data, while Neural Networks include more than 70%. This indicates the model structure is an important source of uncertainty of hydrologic modeling and needs to be evaluated carefully. Further exploitation of the effect of different treatments of the uncertainties of model structures on hydrologic modeling was conducted through applying four types of Bayesian Neural Networks. By considering uncertainty associated with model structure, the Bayesian Neural Networks can provide more reasonable quantification of the uncertainty of streamflow simulation. This study stresses the need for improving understanding and quantifying methods of different uncertainty sources for effective estimation of uncertainty of hydrologic simulation.