Croatia’s number one Marin Cilic then prevailed 4-6 6-3 6-7(3) (6-1) 8-6 over a gallant Mardy Fish, who was brought into the US team to cover injured Wimbledon finalist Andy Roddick.
After narrowly winning the first set, 17th-ranked Blake broke Karlovic early in the second to rush to a two-set lead.
But the towering Croat clubbed three winners to break Blake in the second game of the third set, and closed it out as his serve and volleying came to the fore.
Karlovic took the fourth in a tie-break then broke his opponent in the 12th game of the final set to make sure of the result.
“I was a bit nervous at the start, playing before the home crowd, but I became more relaxed as the match went on, and I managed to turn it around. This is surely one of the biggest matches in my career,” Karlovic said.
After losing the first set in a hail of unforced errors and poor serving, world number 15 Cilic broke Fish twice in the second to square the ledger.
After losing the third in a tie-break, Cilic appeared to have all the momentum going into the decider, steamrolling Fish 6-1 in the fourth, but the American dug deep, breaking back after surrendering his serve at 4-3 in the fifth.
Fish eventually capitulated in the 14th game, however, to put the hosts in the box seat ahead of the doubles.