The half-metallic CrO2 with nearly 100% spin polarization is an ideal system to study magnetic domain-wall resistance, which differs from the resistance (or resistivity) inside a single domain. To experimentally measure the domain-wall resistance, we design and prepare a special CrO2 epitaxial nanostructure with an asymmetrical weak link to localize a domain wall, by using the techniques of chemical vapor deposition and selective-area growth. This structure provides a capability to generate and annihilate a domain wall near the weak link. By contrasting the resistance between a single-domain state and a domain-wall state, we observe a repeatable and reversible resistance jump, namely domain-wall resistance, in half-metallic CrO2. Using the Levy-Zhang model, we further obtain the spin asymmetry ratio ρ0↑/ρ0↓ between resistivities in the two spin channels. The ratio, 4256 ± 388 at 5.0 K, is much larger than that of conventional ferromagnetic metals, attesting to the half metallicity of CrO2.