"It's been a long road," Johnson said. "I guess the one word that would sum it all up is that I've persevered."
Johnson allowed only an unearned run and threw 50 of his 78 pitches for strikes. He faced four batters above the minimum and got spotless relief from his bullpen.
He left leading 2-1, but nearly wound up with a no-decision. The Nationals loaded the bases with two outs in the eighth before Adam Dunn was called out on strikes with a full count on a knee-high fastball from reliever Brian Wilson.
San Francisco added three runs in the ninth.
Some of the few thousand fans who witnessed Johnson's 300th victory - the Nationals have trouble drawing a crowd for anything these days - chanted "Randy! Randy!" in the bottom of the ninth. When the game was over, he gave hugs to teenage son Tanner, who served as a Giants batboy, as well as his teammates. Johnson then tipped his hat to the cheering crowd before disappearing into the dugout.
"It's nice to have this moment with my family and friends that came," Johnson said. "It's the coolest moment to be able to share something with my son. I'm just sad my dad wasn't here. He wasn't able to see my games the last 17 years, but he's up there watching."
Johnson (5-4) became the sixth left-hander to win 300 games, and the first pitcher to do it on his first try since Tom Seaver in 1985.
The 45-year-old Johnson is the second-oldest pitcher to reach the milestone. Knuckleballer Phil Niekro was 46 when he won his 300th with the New York Yankees in 1985.
Afterward, Johnson said he was "exhausted."
"But I don't think my work's done here yet. I didn't come here to just win five games," he added.
As long as it took to get to 300, the final step for Johnson required quite a bit of patience. Two off days in the Giants' schedule and a rainout Wednesday night gave him seven days of rest since winning No. 299 last week against Atlanta. In addition, Thursday's game was delayed 36 minutes by bad weather and was played in a light rain.
Once he finally got on the mound, Johnson had an efficient outing - but not flashy. He didn't allow a baserunner until a walk in the fourth inning and didn't give up a hit until Elijah Dukes' broken-bat single up the middle in the fifth.
Johnson then walked Austin Kearns, putting runners on first and second with none out. But second baseman Emmanuel Burriss thwarted a rally with the defensive play of the game. On a one-hopper that hit the mound, Burriss dived to his right to stab the ball backhanded, then flipped it out of his glove to shortstop Edgar Renteria to start a dazzling double play.
"That could have turned the game around for them, easily," Johnson said.
The 6-foot-10 Johnson hit the turf himself after a comebacker that he knocked down in the sixth, barehanding the ball while falling forward to throw out pinch-hitter Anderson Hernandez. The Nationals scored their only run later in the inning, after Renteria's throwing error allowed Alberto Gonzalez to reach. Gonzalez was doubled home by Nick Johnson.
Randy Johnson got the run support he needed early, when Juan Uribe's RBI grounder and Burriss' RBI single off Jordan Zimmermann (2-3) gave the Giants a 2-0 lead in the second.
After Johnson was pulled, relievers Brandon Medders, Jeremy Affeldt and Wilson took care of the rest, although Wilson's strikeout of Dunn was a borderline call disputed by the Nationals slugger. Wilson also worked the ninth for his 13th save.
Several hundred were in the ballpark when the national anthem was sung at 5:03 p.m., with the biggest cluster surrounding the Giants bullpen in left field, where Johnson had been warming up.
Johnson joined Steve Carlton as the only pitchers to win No. 300 against the organization with whom they made their major league debut. Carlton started with St. Louis on April 12, 1965, then beat the Cardinals on Sept. 23, 1983, at age 38 while with the Phillies.
Johnson's first three wins - exactly 1 percent of his total - came with the Montreal Expos, long before the franchise moved to Washington. His first victory was Sept. 15, 1988, five days after his 25th birthday, but most people noticed him only because he was the tallest player in the majors.
Notes: Johnson is the fourth pitcher to win his 300th with the Giants, joining Christy Mathewson in 1912 and Tim Keefe and Mickey Welch, both in 1890. ... The Nationals have lost seven of eight. ... Washington OF Josh Willingham remained sidelined with a stomach virus.
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