Smart multi-walled carbon nanotube (MWCNT)-coated cellulose fibers with a unique sensing ability were manufactured by a simple dip coating process. The formation of electrically-conducting MWCNT networks on cellulose mono-and multi-filament fiber surfaces was confirmed by electrical resistance measurements and visualized by scanning electron microscopy. The interaction between MWCNT networks and cellulose fiber was investigated by Raman spectroscopy. The piezoresistivity of these fibers for strain sensing was investigated. The MWCNT-coated cellulose fibers exhibited a unique linear strain-dependent electrical resistance change up to 18% strain, with good reversibility and repeatability. In addition, the sensing behavior of these fibers to volatile molecules (including vapors of methanol, ethanol, acetone, chloroform and tetrahydrofuran) was investigated. The results revealed a rapid response, high sensitivity and good reproducibility for these chemical vapors. Besides, they showed good selectivity to different vapors. It is suggested that the intrinsic physical and chemical features of cellulose fiber, well-formed MWCNT networks and favorable MWCNT-cellulose interaction caused the unique and excellent sensing ability of the MWCNT-coated cellulose fibers, which have the potential to be used as smart materials.