The aquaglyceroporin from Plasmodium falciparum (PfAQP) is a potential drug target for the treatment of malaria. It efficiently conducts water and other small solutes, and is proposed to intervene in several crucial physiological processes during the parasitic life cycle. Despite the wealth of experimental data available, a dynamical and energetic description at the single-molecule level of the solute permeation through PfAQP has been lacking so far. Here we address this question by using equilibrium and umbrella sampling molecular dynamics simulations. We computed the water osmotic permeability coefficient, the pore geometry and the potential of mean force for the permeation of water, glycerol and urea. Our simulations show that the PfAQP, the human aquaporin 1 (hAQP1) and the Escherichia coli glycerol facilitator (GlpF) have nearly identical water permeabilities. The Arg196 residue at the ar/R region was found to play a crucial role regulating the permeation of water, glycerol and urea. The computed free energy barriers at the ar/R selectivity filter corroborate that PfAQP conducts glycerol at higher rates than urea, and suggest that PfAQP is a more efficient glycerol and urea channel than GlpF. Our results are consistent with a solute permeation mechanism for PfAQP which is similar to the one established for other members of the aquaglyceroporin family. In this mechanism, hydrophobic regions near the NPA motifs are the main water rate limiting barriers, and the replacement of water–arg196 interactions and solute-matching in the hydrophobic pocket at the ar/R region are the main determinants underlying selectivity for the permeation of solutes like glycerol and urea.