Studies of fossil hominin hands are important for understanding the selective pressures that have ultimately culminated in the observed dexterity of the modern human hand. However, the extent to whichexternal morphology correlates with measures of the internal structure of hand bones, and how these in turn are related to mechanical loading during life, is poorly understood. Here we analyse the external shape and cross-sectional geometry of the first metacarpal (Mc1) in a sample of geographically and temporally diverse Homo sapiens and a Homo neanderthalensis specimen. The recent modern human sample (n=24) includes: pre-industrial humans from America, Australia, the Chatham Islands, and Egypt; post-industrial humans from an 18-19th Century German cemetery; and humans from the medieval shipwreck of the Mary Rose, where all individuals are assumed to be males that were melee infantry, archers, gunners or mariners. The fossil Homo sapiens specimens (Qafzeh 9 and Arene Candide 2) and the Neanderthal specimen (Kebara 2), are all thought to have engaged in more intense manual activity than recent humans. It is hypothesised that the pre-industrial humans, Mary Rose individuals, fossil H.sapiens and the Neanderthal will exhibit greater shape and cortical robusticity of the Mc1 than the post-industrial modern human group. 3D surface models and cross-sections of each Mc1 were obtained from micro computed tomography/X-ray microscopy scans. 3D anatomical and sliding semi-landmarks were used to perform a geometric morphometric (GM) analysis of Mc1 articular surface and diaphyseal shape (using the Morpho package in R). Using BoneJ, cross-sections at 33%, 50% and 66% of diaphysis length were analysed to measure cross sectional area (CSA) and the second polar moment of area (J). Principal component analysis (PCA) was carried out on both the 3D GM data and the cross-sectional geometry (CSG) variables, respectively. CSA and J were both regressed on each of the first three principal components of first metacarpal shape. A PCA of the CSG variables revealed that among the modern human sample the Mary Rose specimens displayed the highest mean levels of CSA and J associated with high resistance to torsional deformation, and inferred intense manual loading of Mc1. The Neanderthal and fossil H. sapiens both closely clustered around the Mary Rose group, suggesting that these fossil individuals were all undertaking similar levels of intense manual activity, which could be driven by the frequent adoption of transverse power-grips. Unexpectedly, the pre-industrial modern humans demonstrated significantly lower values of CSA and J than the Mary Rose sample, and overlapped with only some of the post-industrial modern human samples. A PCA of Mc1 shape revealed morphological similarities across the Mary Rose sample, fossil H. sapiens, the Kebara Neanderthal and some of the post-industrial modern humans. This group appears to share relatively robust Mc1 shafts and enlarged proximal and distal articular surfaces compared with pre-industrial modern humans. The Kebara Neanderthal was also slightly differentiated by the pronounced lateral flange associatedwith the opponens pollicisenthesis. Regressions of cross-sectional geometry variables on Mc1 shape variables revealed a number of significant but relatively weak relationships (R2 values between ~0.16-0.18), indicating a link between aspects of shaft shape and cortical bone distribution. In summary, our results provide further evidence for the impact of manipulative behaviour on thumb shape and structure, yet more investigation is needed to ascertain the exact nature of this relationship.