While short-term disuse negatively affects mechanical muscle function (e.g. isometric muscle strength) little is known of the relative contribution of adaptions in central neural drive and peripheral muscle contractility. The present study investigated the relative contribution of adaptations in central neural drive and peripheral muscle contractility on changes in isometric muscle strength following short-term unilateral disuse (4 days, knee brace) and subsequent active recovery (7 days, one session of resistance training) in young (n = 11, 24 yrs) and old healthy men (n = 11, 67 yrs). Maximal isometric knee extensor strength (MVC) (isokinetic dynamometer), voluntary muscle activation (superimposed twitch technique), and electrically evoked muscle twitch force (single and doublet twitch stimulation) were assessed prior to and after disuse, and after recovery. Following disuse, relative decreases in MVC did not differ statistically between old (16.4 ± 3.7%, p < 0.05) and young (−9.7 ± 2.9%, p < 0.05) (mean ± SE), whereas voluntary muscle activation decreased more (p < 0.05) in old (−8.4 ± 3.5%, p < 0.05) compared to young (−1.1 ± 1.0%, ns) as did peak single (−25.8 ± 6.6%, p < 0.05 vs −7.6 ± 3.3%, p < 0.05) and doublet twitch force (−23.2 ± 5.5%, p < 0.05 vs −2.0 ± 2.6%, ns). All parameters were restored in young following 7 days recovery, whereas MVC and peak twitch force remained suppressed in old. Regression analysis revealed that disuse-induced changes in MVC relied more on changes in single twitch force in young (p < 0.05) and more on changes in voluntary muscle activation in old (p < 0.05), whereas recovery-induced changes in MVC mainly were explained by gains in voluntary muscle activation in both young and old. Altogether, the present data demonstrate that plasticity in voluntary muscle activation (~central neural drive) is a dominant mechanism affecting short-term disuse- and recovery-induced changes in muscle strength in older adults.