The linear calibration model is a powerful statistical tool that can be utilized to predict an unknown response variable, Y, through observations of a proxy or predictor variable, X. Since calibration involves estimation of regression model parameters on the basis of a limited amount of noisy data, an unbiased calibration slope estimation is of utmost importance. This can be achieved by means of state-of-the-art, data-driven statistical techniques. The present paper shows that weighted least-squares for both variables estimation (WLSXY) is able to deliver unbiased slope estimations under heteroscedasticity. In the case of homoscedasticity, besides WLSXY, ordinary least-squares (OLS) estimation with bias correction (OLSBC) also performs well. For achieving unbiasedness, it is further necessary to take the correct regression direction (i.e., of Y on X) into account. The present paper introduces a pairwise moving block bootstrap resampling approach for obtaining accurate estimation confidence intervals (CIs) under real-world climate conditions (i.e., non-Gaussian distributional shapes and autocorrelations in the noise components). A Monte Carlo simulation experiment confirms the feasibility and validity of this approach. The parameter estimates and bootstrap replications serve to predict the response with CIs. The methodological approach to unbiased calibration is illustrated for a paired time series dataset of sea-surface temperature and coral oxygen isotopic composition. Fortran software with implementation of OLSBC and WLSXY accompanies this paper.