After a string of close calls in their 51-season history, Santana finally finished the job in the Mets' 8,020nd game since the team was born in 1962.
He needed a couple of key assists to do it.
Carlos Beltran, back at Citi Field for the first time since the Mets traded him last July, hit a line drive over third base in the sixth inning that hit the foul line and should have been called fair. But third base umpire Adrian Johnson ruled it foul and the no-hitter was intact.
Mike Baxter made a tremendous catch in left field to rob Yadier Molina of extra bases in the seventh, getting injured in the process.
REDS 4, ASTROS 1
HOUSTON (AP) — Jay Bruce homered and drove in two runs to back a solid performance by Mike Leake and the Reds beat the sliding Astros.
Leake (2-5) had a season-high seven strikeouts in seven innings, yielding just one run and four hits. Aroldis Chapman struck out the side in the ninth for his fourth save.
Houston has dropped seven straight in its longest skid since it lost seven in a row last August.
Joey Votto hit a two-out single in the first and scored on Brandon Phillips' double off the wall in centre, putting Cincinnati up 1-0. Bruce then singled in Phillips.
Houston starter J.A. Happ (4-5) allowed three runs and five hits in seven innings.
PIRATES 8, BREWERS 2
MILWAUKEE (AP) — The Pirates scored six runs off Randy Wolf in the third inning, then went on to pound the Brewers.
Ryan Braun left the game with a right hip strain, after sitting out Thursday night's game because of lingering tightness in his right Achilles tendon.
Kevin Correia (2-5) gave up two runs and five hits in 5 2-3 innings for the Pirates, who have won six of their last seven games. The Pirates came into Friday's game with a 4-38 record at Miller Park since the start of the 2007 season.
Nyjer Morgan hit a solo home run in the first inning for Milwaukee, snapping his Major League record of 138 straight plate appearances without an RBI to start the season. But Morgan's misplayed ball in the outfield played a critical role in the Pirates' big inning.
PHILLIES 6, MARLINS 4
PHILADELPHIA (AP) — Hunter Pence hit a two-run homer, Hector Luna had three RBIs and the Phillies beat the Marlins.
Pence, Carlos Ruiz and Placido Polanco each had three hits as the Phillies won for the seventh time in nine games. Jonathan Papelbon got five outs for his 15th save in 15 chances.
Kyle Kendrick (2-4) allowed eight hits in 5 1-3 innings, but held Miami to two runs.
Mark Buehrle (5-5) gave up four runs and a season-high 11 hits in five innings for the Marlins. He had won his last four decisions.
PADRES 7, DIAMONDBACKS 1
SAN DIEGO (AP) — Jesus Guzman's pinch-hit two-run homer ignited a sixth-run eighth inning and lifted the Padres to a win over the Diamondbacks.
Guzman's shot broke a 1-all tie as San Diego sent 11 batters to the plate in the eighth off three pitchers. He connected on a 1-1 changeup off rookie Wade Miley (6-2) into the left-field stands to help the Padres snapped a six-game losing streak
San Diego had managed just three hits off Miley heading into the eighth before Alexi Amarista reached on a one-out bunt single that brought up Guzman.
Andrew Cashner (3-3) pitched the eighth for San Diego, which was coming off a 1-9 road trip. The Padres have worst record in the majors at 18-35.
ROCKIES 13, DODGERS 3
DENVER (AP) — Wilin Rosario hit a two-run homer and the Rockies took advantage of four Dodgers errors to romp past Los Angeles for its season-high fifth straight win.
Pinch hitter Chris Nelson and Michael Cuddyer added back-to-back solo homers off reliever Josh Lindblom in the eighth inning. Colorado scored four unearned runs and sent the Dodgers to their fifth loss in a row.
Dexter Fowler added three hits and two RBIs and Carlos Gonzalez had two hits and drove in a run. The Rockies are averaging 10.6 runs during their winning streak.
GIANTS 4, CUBS 3
SAN FRANCISCO (AP) — Melky Cabrera remained the hottest hitter in the National League, Madison Bumgarner picked up his first win in nearly four weeks and the Giants beat the Cubs.
Cabrera had two hits to raise his average to .376, tying him with Paul Konerko of the Chicago White Sox for the highest mark in the majors. That comes on the heels of his outstanding May when he tied a San Francisco franchise record with 51 hits.
Ryan Theriot added three hits and scored twice while Buster Posey had two RBIs to give the Giants their fourth win in five games on the current homestand.
Alfonso Soriano hit a three-run home run in the ninth for Chicago, but the Cubs fell short and lost for the 15th time in their last 20 games.