The potent combination has the team off to its best start in 65 years.
Ludwick and Chris Duncan also connected off Jordan Zimmermann, giving St. Louis homers from its 3-4-5 hitters off the rookie right-hander in his first career loss. Joe Thurston later added his first major league home run for St. Louis, which has won three in a row and nine of 11 overall.
"I feel like the middle of the order has been doing good, but I feel like the whole lineup has been doing a good job," Ludwick said. "I think we're still one of the top offensive leaders in baseball. Combine that with the pitching we're getting and it's a deadly combination."
The Cardinals' 17-7 start is their best since 1944 and they wasted no time in providing Wellemeyer an early lead against the Nationals, whose 5-17 mark is the worst in the majors.
"The main thing is to go out and try to do as much damage as we can," Pujols said. "Anytime you can give a lead to the pitcher, he would love to take it. It gives him something to work on."
Wellemeyer (2-2) allowed two runs on six hits, walked two and struck out three.
"He got into an early grove, and just concentrated great," Cardinals manager Tony LaRussa said. "Lately, he's had some periods, especially early, where he wasn't quite right. He had to compete hard to stay in the game."
The right-hander hopes Friday's start is a repeat of last May, when he went 4-0 and was named the pitcher of the month in the National League.
"May last year was excellent to me, so keep it going," Wellemeyer said.
Ryan Zimmerman singled in the third, extending his hitting streak to a Nationals-record 20 games. It's the longest streak in the majors this season.
Pujols gave the Cardinals a 1-0 lead in the first on his ninth homer, a towering shot down the left-field line.
A two-run homer by Duncan extended the lead to 3-0 in the fourth. Pujols hit a leadoff double before Duncan sent a 1-0 fastball from Zimmermann (2-1) into the stands in right-center.
In the sixth, Ludwick followed Pujols' third hit of the game with his sixth homer, ending an 0-for-13 skid.
"He's not perfect and he missed with his location a few times," Nationals manager Manny Acta said of Zimmermann. "It happened that every time he missed, the ball went out of the ballpark. He went after them, and that's what we like."
Zimmermann, one of the top young pitching prospects in baseball, allowed five runs and eight hits in 5 2-3 innings. He walked none and struck out six.
"Up here, they don't miss hardly as much as they do [in the minors]," said Zimmermann, who had yielded one homer over 11 1-3 innings in his first two starts. "You can't make those mistakes up here."
Thurston lined a homer inside the right-field foul pole in the seventh off Logan Kensing.
St. Louis 2B Skip Schumaker went 0 for 5, ending his hitting streak at a career-best 11 games. ... Cardinals starting pitchers have allowed only five homers this season. ... The last 20-game hitting streak by a Washington, D.C.-based player came in 1953 by the Washington Senators' Mickey Vernon. ... Flores has tripled on consecutive nights after having one triple in his first 187 career games.