The study was conducted to contrast exertion-dependent changes in electromyography (EMG), force fluctuation (FF), and limb acceleration (LA) during isometric contraction to attain a versatile picture of muscle fatigue. Fifteen volunteers performed sustained index abduction at 25 and 75% maximal voluntary contractions (MVC) until failure at the tasks; meanwhile, changes in temporal/spectral features of force, muscle activity of the first dorsal interosseous (FDI), and acceleration of the index and hand were monitored. The results showed a manifest increase in all recorded signals for the 25% MVC paradigm, especially for LA, which demonstrated the largest increment in amplitude. In addition to progressive enhancement of the mechanical coupling of the metacarpophalangeal (MCP) joint, the 25% MVC paradigm added to EMG-FF and EMG-LA coherences (CohEMG-FF and CohEMG-LA) at 8-12 Hz and the shift of the spectral peak of the LA to higher frequencies. In contrast, the 75% MVC paradigm did not modulate significantly the spectral peak of LA. Also, CohEMG-FF, CohEMG-LA at 8-12 Hz, and the mechanical coupling of the MCP joint, were conversely undermined consequent to the high exertion paradigm. The present study suggests that LA was most susceptible to muscle fatigue following sustained contraction at a lower exertion level, and diverging alternations among various physiological signals ascribed to exertion-dependent contributions of central and peripheral origins to muscle fatigue.