This paper presents a novel approach for simulation validation by combining systematic, National Institute of Standards and Technology-guideline-based uncertainty assessment with the gamma dose distribution comparison method, and applies the approach to simulated and measured complicated pressure distributions in the field of focused ultrasound. Simulations require verification and validation to demonstrate that they correctly implement the underlying model and sufficiently capture the real-world behavior of the system of interest within the context-of-use. Uncertainty assessment is necessary to determine the quality (strength, success, and range) of the validation. The combined approach of systematic uncertainty evaluation and the gamma-method presented herein permits thorough validation with meaningful and reasonable tolerances (expanded uncertainty: 1.04 dB = 12.7%, 1.88 wavelengths), whereas point-wise comparison would have resulted in an unacceptably large uncertainty (>10 dB) due to the impact of distortion. The approach presented also provides a scalar agreement metric and a natural means of visualizing areas of disagreement. Verification is achieved by identifying the critical physical and numerical phenomena and ascertaining correct handling by means of analytical and numerical benchmarks. The generality of the verification and validation approach presented makes it applicable to a wide range of computational models, beyond the highlighted acoustic simulations.