Harper missed four consecutive games, and Segura was on the IL with a right quad strain. Both are starting in Friday night's National League East matchup against the Atlanta Braves.
The Phillies are in first place after a four-game sweep of the Milwaukee Brewers. Manager Joe Girardi said he hopes the healthy lineup adds to the team's momentum.
"I'm excited to have them both back," Girardi said before Friday's game. "They both, before they went down, were swinging the bat great. Obviously they're staples in our lineup that we've been missing."
Girardi said Harper "felt comfortable enough that he was ready to go" but couldn't say the right fielder has fully recovered from his wrist injury.
"I think it feels pretty good, but it's like what happens if he takes a swing and it's funny," Girardi said, adding, "Just hope he doesn't fall backward again."
Outfielder Mickey Moniak, who was hitting .120, was optioned to Triple-A Lehigh Valley to clear a roster spot for Segura.