Walker hit a three-run homer and the 43-year-old Colon won for the fifth time in his last six decisions as the Mets opened their second half of their season with a 5-3 victory over the Philadelphia Phillies on Friday night.
Juan Lagares added a solo homer for the Mets, who snapped a three-game losing streak.
Walker said the first game after the All-Star break is "one of the hardest games of the year," since players often struggle to regain their rhythm.
"But sometimes if you can get a big hit, like a home run," he said, "it eases the tension a little bit."
His three-run shot in the sixth inning off Jeremy Hellickson (6-7) gave the Mets a 4-0 lead. It was Walker's 16th homer of the season, matching his total for all last season in Pittsburgh, and his fourth in as many games in Citizens Bank Park.
Colon (8-4), who retired the first 13 hitters he faced, worked 5 2/3 innings and allowed three unearned runs and four hits while striking out four and walking two.
"He's not the guy I wanted to see, coming out of the break, because he's such a good pitcher," Phillies manager Pete Mackanin said. "He knows what he's doing, and he just kind of stifled us for a while there."
Colon needed just 35 pitches to negotiate the first four innings, and in all fired 52 strikes among his 78 offerings.
"Everything worked out," he said. "Around the fifth or sixth inning, I just got a little tired."
He departed amid the Phillies' three-run sixth inning, but four Mets relievers combined for 3 1/3 scoreless innings.
Jeurys Familia, the last of those, worked a perfect ninth to post his 32nd save. Familia, who leads the major leagues in that category, has converted his last 48 regular-season save opportunities.
The Phillies, who managed just five hits, lost for only the fourth time in their last 14 games.
"It's not the way we wanted to start the homestand," said Mackanin, whose team played the first of seven games in its own park. "All in all, needed a few more hits."
Hellickson went six innings and allowed four runs and seven hits while striking out five. He did not walk a batter.
Lagares hit his first pitch of the third inning, a fastball, into the seats in center field, his third homer of the season.
The Mets' Asdrubel Cabrera and Curtis Granderson opened the sixth with singles, and Walker then drove Hellickson's 3-2 fastball into the seats in left, making it 4-0.
Hellickson said the pitch was "a little up," and added that he grew "a little gassed" toward the end of his outing.
"I was working way too hard the last two innings," he said.
Philadelphia answered with three unearned runs off Colon in the bottom of the sixth. Odubel Herrera reached on an error with one out and scored on Peter Bourjos' triple. Bourjos then came home on a groundout by Maikel Franco, and with two outs, Cody Asche's RBI single delivered Tommy Joseph, slicing the Mets' lead to 4-3.
Lagares led off the seventh by drawing a walk from reliever Andrew Bailey, then stole second and went to third on a flyout by Alejandro DeAza. Jose Reyes, batting against a drawn-in infield, then bounced a ball over the mound that was fielded on the move by Freddy Galvis, the Phillies' shortstop.
He threw high to Cameron Rupp, the Philadelphia catcher, and Lagares slid under the tag to give New York a 5-3 cushion.
NOTES: Mets OF Yoenis Cespedes missed his third straight game with a strained right quadriceps muscle, and he and manager Terry Collins said before the game he is day to day, according to MLB.com. ... Philadelphia C Cameron Rupp began the night with the highest slugging percentage among major league catchers since June 1 (.632). It is nonetheless unclear where he fits in the club's long-range picture because the Phillies are high on some receivers in their minor league chain, notably Jorge Alfaro, who is currently at Double-A Reading. Rupp is unbothered by all the talk. "It's just noise," he said before the game. "I look at it as, it doesn't matter how long I've been in the big leagues or how long my contract, whatever it is; somebody's trying to take my spot. Whether I've established myself or not, I've still got to go out and play, and I've got to have results. ... Phillies 3B Maikel Franco went 0-for-4, ending a 10-game hitting streak. ... Philadelphia RF Peter Bourjos has reached base in 22 consecutive games, the longest streak by a Phillie this season. ... The 48 consecutive saves converted by Mets RHP Jeurys Familia is the fifth-longest streak in major league history. John Axford is fourth, with 49.