The California-based airline's arrival at O'Hare means only one major domestic airline is not serving the Chicago market.
O'Hare currently offers nonstop service to 198 cities worldwide and has 52 airlines operating flights from 189 gates.
Virgin American will use one of 11 gates the city recently acquired from Delta Airlines by the city in O'Hare's Terminal 3. Six of those gates will go to American Airlines.