The independent agency has been in talks with National Express since it worked on a project for the coach operator last year. The agency was permanently appointed on Friday, taking over from McCann Birmingham.
Isobel was first hired in 2013 by National Express, the largest scheduled coach operator in the UK, to work on a summer project called "instant getaways" following a four-way pitch run by AAR.
The campaign featured summer snaps and was designed to encourage people to travel by coach during the summer months.
Paul Houlding, the managing partner at Isobel, said: "National Express is a joy to work with. They have a good product and huge ambition. Our task is to help them realise those ambitions by changing people’s perceptions of the brand and creating a whole new generation of coach travellers."
Isobel said its first print and digital work for National Express, under its new account, should be out later this month, with television work coming out in mid-June.
Susanna Holdsworth, the marketing director at National Express, said: "Isobel has demonstrated a thorough understanding of our brand and business and have come up with a great new campaign that we are all very excited about."
National Express appointed AIS London to its consolidated CRM account in January, citing a wish to develop a more strategic approach to CRM. AIS London took over from Sky IQ, CheetahMail and McCann Birmingham.