The service is the airliner’s sixth low-fare route from Birmingham, joining Bucharest, Budapest, Poznan, Warsaw and Wroclaw.
The Central and Eastern European (CEE) region offers huge potential for British businesses looking to expand into new markets.
According to UKTI, UK exports to the region are worth over £16bn annually, with goods exports doubling over the past decade, and services exports - over £4bn - trebling.
William Pearson, aviation development director at Birmingham Airport, said: "This news has really got 2016 off to a great start.
“We're very excited about Wizz Air's growth at Birmingham and delighted to see Sofia being added to the growing route network available from Birmingham.
“Having launched only in September with flights to Warsaw and Budapest, the carrier has since launched flights to Poznan and will be operating to Wroclaw, Bucharest and Sofia from the summer, as well as increasing services to the popular city of Budapest from two to three times weekly.”
Christine Hamilton, interim regional director of UKTI West Midlands, welcomed the new route, saying that with exports from the West Midlands to Bulgaria growing by almost 70% between 2011 and 2014, it demonstrates that there is potential for further growth.
"The opening of another route from Birmingham International Airport can only be good news for our region," she said. "Businesses already exporting to the market are able to visit their customers more easily, while those looking to explore opportunities there will find it easier to reach potential customers."
Tickets are now on sale via the Wizz Air website.