Hopman Cup debutant Jiri Vesely (22), from the Czech Republic, stormed to a 4-0 lead in the first set before 34-year-old Hewitt started his comeback and won the next two games to eventually go down 3-6.
The second set went on serve forcing a tie-break that Hewitt won convincingly.
The Perth crowd was well and truly behind the eight-time Hopman Cup player and 2003 finalist but a victorious last hurrah at the Perth Arena was not meant to be. He went down 3-6, 7-6, 4-6 to the left-handed, 198cm Czech.
Get in front of tomorrow's news for FREE
Journalism for the curious Australian across politics, business, culture and opinion.
READ NOW“I got better as the match went on… I haven’t played competition singles since the US Open,” Hewitt said. “He’s (Jiri) a quality player, he’s got a big first and second serve.”
Hewitt’s Australia Gold partner Jarmila Wolfe (28) lost 5-7, 3-6 against Karolina Pliskova (23) and the Australian duo went down 2-6, 5-7 in the mixed doubles.
Earlier in the day, Kyrgios required three sets to beat 18-year-old German Alexander Zverev in 35C heat.
The first set started on serve until Zverev, whose serve rarely dropped below 210km/h, broke the Australian’s serve to lead 5-3, eventually taking the first set 6-4.
Kyrgios dominated the second set 6-1 and broke Zverev’s serve to be 5-3 in the third, eventually winning 6-4.
“It’s good to start the year with a win,” Kyrgios said.
Kyrgios said he was looking forward to playing Great Britain’s Andy Murray on Wednesday night.
Gavrilova got Australia Green off to a winning start before the men’s match, beating Sabine Lisicki (26) 6-2 6-2.
The Australia duo made it a clean sweep, beating the Germans 6-3 4-6 10-7 in the mixed doubles.