This retrospective study aimed to develop and validate deep-learning-based models for grading clear cell renal cell carcinoma (ccRCC) patients. A cohort enrolling 706 patients (n = 706) with pathologically verified ccRCC was used in this study. A temporal split was applied to verify our models: the first 83.9% of the cases (years 2010–2017) for development and the last 16.1% (year 2018–2019) for validation (development cohort: n = 592; validation cohort: n = 114). Here, we demonstrated a deep learning(DL) framework initialized by a self-supervised pre-training method, developed with the addition of mixed loss strategy and sample reweighting to identify patients with high grade for ccRCC. Four types of DL networks were developed separately and further combined with different weights for better prediction. The single DL model achieved up to an area under curve (AUC) of 0.864 in the validation cohort, while the ensembled model yielded the best predictive performance with an AUC of 0.882. These findings confirms that our DL approach performs either favorably or comparably in terms of grade assessment of ccRCC with biopsies whilst enjoying the non-invasive and labor-saving property.