Understanding the dominant direction of association between cardiorespiratory fitness (CRF) and grip strength could help refine physical activity recommendations. We performed a Mendelian Randomization (MR) analysis to elucidate the bidirectional relationship between CRF and grip strength (GS). Using an inverse‐variance weighted (IVW) MR framework, we estimated the strength of the GS (exposure)‐CRF (outcome) association using genome‐wide association summary data. When examining the CRF (exposure)‐GS (outcome) association, the CRF genetic instrument was related to individual‐level GS phenotypic data in 367 693 UK Biobank participants. Several sensitivity analyses were performed (e.g., MR‐Egger, MR‐weighted median estimator and MR‐PRESSO) and both measures were scaled by body weight (w). In the direction GS‐to‐CRF, a 1‐unit increase in GSw (i.e., GS/weight) was associated with 1.70 mL/kg/min (95% confidence interval (CI): 1.14,2.27) higher CRFw (IVW model). This finding persisted across most sensitivity analyses. In the reverse direction, there was no evidence supporting an effect of CRFw on GSw, e.g., a 1‐unit increase in CRFw led to a 0.00 kg/kg (95% CI: −0.01,0.02) higher GSw (IVW model). Our finding of a dominant direction of association from greater GS to higher CRF is relevant when considering how to promote physical activity guidelines. For example, placing too much emphasis on improving/maintaining CRF is unlikely to result in maximum benefits for other fundamental components of physical fitness, particularly muscle strength.