After two losses to the Los Angeles Dodgers in Australia, they truly open at home Monday against the San Francisco Giants.
Left-hander Madison Bumgarner, an All-Star last season, makes his first opening-day start for the Giants and Brandon McCarthy starts for the Diamondbacks.
The four-game series features two teams that will try to unseat the favored Dodgers in the NL West.
San Francisco won the division title and the World Series two years ago, a year after the Diamondbacks finished atop the NL West.
Arizona has been hit by significant injuries to its top starting pitcher, Patrick Corbin, and its bullpen setup man, David Hernandez.
''Virtually every team is going to have obstacles,'' manager Kirk Gibson said. ''We've had some hit us early. We'll be resilient. We'll have to fight through it.''
New Arizona closer Addison Reed said there's no way to avoid the kind of injuries Corbin and Hernandez sustained.
''But our farm system is deep,'' he said. ''So many guys we can plug in.''
Bumgarner, at 24 the youngest of the San Francisco starters, was 13-9 with a 2.77 ERA in 31 starts last season. As usual, starting pitching is the Giants' strength, with a rotation that includes Matt Cain, Tim Lincecum and 38-year-old newcomer Tim Hudson.
The Giants (76-86) finished third in the NL West last season, behind the Dodgers and Diamondbacks.
''There's a bad taste in everybody's mouths,'' San Francisco catcher Buster Posey said.
San Francisco had a hard time scoring last year.
''We've got to pick it up here,'' manager Bruce Bochy said. ''This is going to be a big road trip for us. We've got to have these bats going.''
San Francisco needs output from speedy center fielder Angel Pagan, who was bothered by a sore back during spring training.
Wade Miley and Trevor Cahill started in Australia. Miley was solid but not as good as reigning NL Cy Young Award winner Clayton Kershaw in a 3-1 opening defeat, and Cahill was hit hard in a 7-5 loss.
Miley and Cahill will start the second and third games of the Arizona series, while newcomer Bronson Arroyo, sidelined by a sore back during much of spring training, is to start the series finale.
The Giants will go with Cain, Hudson and Lincecum.
McCarthy struggled with injuries last season, going 5-11 with a 4.53 ERA, but had a strong exhibition season. It's his second start in a home opener.
''It's a cool opportunity,''' he said. ''It's always a first chance for the fans to get out and see the guys again. There's always a lot of atmosphere there. It's the closest you get to a playoff atmosphere in the regular season until the season starts drawing to an end. It's a fun challenge.''
Arizona will open with rookie Chris Owings at shortstop. The Pacific Coast League player of the year last season beat out Didi Gregorius, who was optioned to Triple-A Reno.
Arizona, led by NL home run and RBIs leader Paul Goldschmidt, finished 81-81 for the second year in a row in a season slowed by injuries.
''We've already had two games under our belt, but the Giants are always a very good ballclub and play us tough,'' Diamondbacks general manager Kevin Towers said. ''Hopefully the adrenalin will be flowing and McCarthy will have his A-game going.''
Bochy doesn't expect the Diamondbacks to have any hangover from their Sydney sojourn.
''They've had time to recuperate and recover,'' Bochy said. ''That's what they made sure of when they made they made this trip that they could come back. I don't see any difference playing them after going to Australia.''