Industrial production of bacterial cellulose (BC) remains challenging due to significant production costs, including the choice of appropriate growth media. This research focuses on optimization of cheese whey (CW) based media for enhanced production of BC. Two modifications were made for CW medium for BC production with Komagataeibacter rhaeticus MSCL 1463. BC production in a medium of enzymatically hydrolyzed CW (final concentration of monosaccharides: glucose 0.13 g L−1, galactose 1.24 g L−1) was significantly enhanced, achieving a yield of 4.95 ± 0.25 g L−1, which markedly surpasses the yields obtained with the standard Hestrin-Schramm (HS) medium containing 20 g L−1 glucose and acid-hydrolyzed CW (final concentration of monosaccharides: glucose 1.15 g L−1, galactose 2.01 g L−1), which yielded 3.29 ± 0.12 g L−1 and 1.01 ± 0.14 g L−1, respectively. We explored the synergistic effects of combining CW with various agricultural by-products (corn steep liquor (CSL), apple juice, and sugar beet molasses). Notably, the supplementation with 15% corn steep liquor significantly enhanced BC productivity, achieving 6.97 ± 0.17 g L−1. A comprehensive analysis of the BC's physical and mechanical properties indicated significant alterations in fiber diameter (62–167 nm), crystallinity index (71.1–85.9%), and specific strength (35–82 MPa × cm3 g−1), as well as changes in the density (1.1–1.4 g cm−3). Hydrolyzed CW medium supplemented by CSL could be used for effective production of BC.