Before launching his own label, Varvatos was head of menswear design at Calvin Klein and across all Polo Ralph Lauren brands, and created the Polo Jeans Company. His debut line arrived in 2000 — a deliberately "black-less collection" — and his first boutique opened in SoHo that October. In 2008 he opened a store at 315 Bowery, the former home of the rock landmark CBGB, preserving its allure and hosting free monthly concerts.
The brand earned early acclaim — the CFDA's Perry Ellis Newcomer's Award (2000), Designer of the Year (2001) and Menswear Designer of the Year (2005), plus GQ's Designer of the Year (2007). Lion Capital took a majority stake in 2012, with Varvatos remaining Chairman and Chief Creative Officer. Its lines have included John Varvatos Star USA Luxe and the long-running Converse by John Varvatos partnership.