The present invention utilizes multiple A/D (analog-to-digital) paths and cross-path calibration to provide accurate and reliable measurements for each input channel in a data acquisition system. When the system and method are applied, user and automated methods of selecting among a number of alternative input range settings can be reduced, or even eliminated. That is, there is a significant reduction or complete elimination of input range settings in a measurement system. For each measurement channel of interest, the input signal is directed to at least two paths, e.g., Path A and Path B. The first path measures the full range (e.g., +/-10 volts), while the second path includes a high-gain amplifier. Each path includes an analog-to-digital converter (ADC), so that there is a one-to-one correspondence between the number of paths and the number of ADCs, which sample the input signal simultaneously.