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, winning the next two games to eventually go down 6-3.
The second set went on serve forcing a tiebreak 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.
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READ NOWHe went down 6-3 7-6 6-4 against the left handed, 198cm Czech.
“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 7-5 6-3 against Karolina Pliskova (23) and the Australian duo went down 6-2 7-5 in the mixed doubles.
Earlier in the day, Kyrgios took 18-year-old German Alexander Zverev to three sets 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.
“We’ve both got big serves so that (a quick game) was always going to happen.”
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.