The MultiResolution Land Characteristics (MRLC) consortium’s National Land Cover Database (NLCD) was established as an operational, stakeholder-oriented land cover monitoring program with the release of the NLCD2001 database. Both land cover and land cover change data became available with the release of NLCD2006. Here, we report the land cover and land cover change accuracies for NLCD2021, documenting Level II and I accuracies for the 2016, 2019, and 2021 land cover datasets and 2016–2021 land cover change. An additional objective, not addressed in previous NLCD assessments, is the estimation of the total variance of area estimates, where total variance includes sampling variance and variability in reference label assignment. We estimate the total variance of the area estimates for the stable and change classes targeted by the strata used in the sampling design. For the 16 Level II classes, the overall accuracy (OA) was 73% ± 1% when agreement was defined using only the primary reference class label and 89% ± 0.7% when agreement was defined as a match between the map label and either the primary or alternate reference label (± standard error, SE). For the eight Level I classes, the corresponding OA estimates were 81% ± 0.9% and 89% ± 0.7%. Level II and Level I OA tended to be higher for 2016 land cover and lower and more similar for 2019 and 2021 land cover. Land cover change user and producer accuracies (UA and PA) tended to be <50%. When the alternate reference label was included in the definition of agreement, exceptions of high class-specific accuracies (≥75%) were more prevalent for PA than UA. The consistency of reference label interpretations was greater for no-change classes than for change classes. The estimates of the total variance incorporating interpreter variability were often smaller than the standard variance estimates, indicating the possibility that the total variance estimator is highly unstable. Further study is needed to improve the utility of this total variance estimator for practical applications.