We present an ab initio modeling framework to simulate Majorana transport in 2D semiconducting materials, paving the way for topological qubits based on 2D nanoribbons. By combining density-functional-theory and quantum transport calculations, we show that the signature of Majorana bound states (MBSs) can be found in 2D material systems as zero-energy modes with peaks in the local density-of-states. The influence of spin-orbit coupling and external magnetic fields on Majorana transport is studied for two relevant 2D materials, WSe2 and PbI2. To illustrate the capabilities of the proposed ab initio platform, a device structure capable of hosting MBSs is created from a PbI2 nanoribbon and carefully investigated. These results are compared to InSb nanowires and used to provide design guidelines for 2D topological qubits.