Starting from the second post-Keplerian (2PK) Hamiltonian describing the conservative part of the two-body dynamics in massless scalar-tensor (ST) theories, we build an effective-one-body (EOB) Hamiltonian which is a ν deformation (where ν=0 is the test mass limit) of the analytically known ST Hamiltonian of a test particle. This ST-EOB Hamiltonian leads to a simple (yet canonically equivalent) formulation of the conservative 2PK two-body problem, but also defines a resummation of the dynamics which is well-suited to ST regimes that depart strongly from general relativity (GR) and which may provide information on the strong field dynamics; in particular, the ST innermost stable circular orbit location and associated orbital frequency. Results will be compared and contrasted with those deduced from the ST-deformation of the (5PN) GR-EOB Hamiltonian previously obtained in [Phys. Rev. D 95, 124054 (2017)PRVDAQ2470-001010.1103/PhysRevD.95.124054].