RegioJet operates a bus from Brno to Karlovy Vary hourly. Tickets cost $7 - $10 and the journey takes 2 h 30 min. 5 other operators also service this route. Alternatively, Czech Railways (ČD) operates a train from Brno to Karlovy Vary hourly. Tickets cost $11 - $17 and the journey takes 2 h 37 min. Czech Railways (ČD) also services this route every 2 hours.
From Brno, AN u hotelu Grand bus to Prague, Prague ÚAN Florenc then bus to Karlovy Vary, Karlovy Vary. 5 h 40 min 18€. From Brno hl.n. train to Praha hl.n. then train to Karlovy Vary. 6 h 53 min 21€. From Brno drive to Karlovy Vary. 3 h 35 min 37€.