Optical coherence tomography (OCT) has become an established clinical routine for the in vivo imaging of the optic nerve head (ONH) tissues, that is crucial in the diagnosis and management of various ocular and neuro-ocular pathologies. However, the presence of speckle noise affects the quality of OCT images and its interpretation. Although recent frame-averaging techniques have shown to enhance OCT image quality, they require longer scanning durations, resulting in patient discomfort. Using a custom deep learning network trained with 2,328 ‘clean B-scans’ (multi-frame B-scans; signal averaged), and their corresponding ‘noisy B-scans’ (clean B-scans + Gaussian noise), we were able to successfully denoise 1,552 unseen single-frame (without signal averaging) B-scans. The denoised B-scans were qualitatively similar to their corresponding multi-frame B-scans, with enhanced visibility of the ONH tissues. The mean signal to noise ratio (SNR) increased from 4.02 ± 0.68 dB (single-frame) to 8.14 ± 1.03 dB (denoised). For all the ONH tissues, the mean contrast to noise ratio (CNR) increased from 3.50 ± 0.56 (single-frame) to 7.63 ± 1.81 (denoised). The mean structural similarity index (MSSIM) increased from 0.13 ± 0.02 (single frame) to 0.65 ± 0.03 (denoised) when compared with the corresponding multi-frame B-scans. Our deep learning algorithm can denoise a single-frame OCT B-scan of the ONH in under 20 ms, thus offering a framework to obtain superior quality OCT B-scans with reduced scanning times and minimal patient discomfort.