The Brighton-based agency is opening a London office that will serve as a base for US-based iCrossing to expand into Europe.
Spannerworks was acquired by the search marketing agency last month.
Arjo Ghosh, chief executive of Spannerworks, said the new office will help the company deal with "requests for integrated global campaigns far more effectively".
The agency has already started this process and is working on iCrossing client STA Travel.
Spannerworks will carry out regional search engine optimisation strategies in the key UK and US territories for the independent travel site.